docling/tests/data/xml/10-1055-a-2308-2290.nxml

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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" article-type="research-article" xml:lang="en" dtd-version="1.3"><?properties open_access?><processing-meta base-tagset="archiving" mathml-version="3.0" table-model="xhtml" tagset-family="jats"><restricted-by>pmc</restricted-by></processing-meta><front><journal-meta><journal-id journal-id-type="nlm-ta">Thromb Haemost</journal-id><journal-id journal-id-type="iso-abbrev">Thromb Haemost</journal-id><journal-id journal-id-type="doi">10.1055/s-00035024</journal-id><journal-title-group><journal-title>Thrombosis and Haemostasis</journal-title></journal-title-group><issn pub-type="ppub">0340-6245</issn><issn pub-type="epub">2567-689X</issn><publisher><publisher-name>Georg Thieme Verlag KG</publisher-name><publisher-loc>R&#x000fc;digerstra&#x000df;e 14, 70469 Stuttgart, Germany</publisher-loc></publisher></journal-meta>
<article-meta><article-id pub-id-type="pmid">38631385</article-id><article-id pub-id-type="pmc">11518617</article-id>
<article-id pub-id-type="doi">10.1055/a-2308-2290</article-id><article-id pub-id-type="publisher-id">TH-23-11-0519</article-id><article-categories><subj-group><subject>Stroke, Systemic or Venous Thromboembolism</subject></subj-group></article-categories><title-group><article-title>The Association between Obstructive Sleep Apnea and Venous Thromboembolism: A Bidirectional Two-Sample Mendelian Randomization Study</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Zhihai</given-names></name><xref rid="AF23110519-1" ref-type="aff">1</xref><xref rid="FN23110519-1" ref-type="fn">*</xref></contrib><contrib contrib-type="author"><name><surname>Zheng</surname><given-names>Zhenzhen</given-names></name><xref rid="AF23110519-2" ref-type="aff">2</xref><xref rid="FN23110519-1" ref-type="fn">*</xref></contrib><contrib contrib-type="author"><name><surname>Pang</surname><given-names>Lingpin</given-names></name><xref rid="AF23110519-1" ref-type="aff">1</xref><xref rid="FN23110519-1" ref-type="fn">*</xref></contrib><contrib contrib-type="author"><name><surname>Fu</surname><given-names>Kaili</given-names></name><xref rid="AF23110519-2" ref-type="aff">2</xref></contrib><contrib contrib-type="author"><name><surname>Cheng</surname><given-names>Junfen</given-names></name><xref rid="AF23110519-2" ref-type="aff">2</xref></contrib><contrib contrib-type="author"><name><surname>Zhong</surname><given-names>Ming</given-names></name><xref rid="AF23110519-1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Song</surname><given-names>Lingyue</given-names></name><xref rid="AF23110519-1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Guo</surname><given-names>Dingyu</given-names></name><xref rid="AF23110519-1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Qiaoyun</given-names></name><xref rid="AF23110519-1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Yanxi</given-names></name><xref rid="AF23110519-1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Lv</surname><given-names>Yongting</given-names></name><xref rid="AF23110519-1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Riken</given-names></name><xref rid="AF23110519-2" ref-type="aff">2</xref><xref rid="CO23110519-1" ref-type="author-notes"/></contrib><contrib contrib-type="author"><name><surname>Sun</surname><given-names>Xishi</given-names></name><xref rid="AF23110519-1" ref-type="aff">1</xref><xref rid="CO23110519-2" ref-type="author-notes"/></contrib></contrib-group><aff id="AF23110519-1"><label>1</label><institution>Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China</institution></aff><aff id="AF23110519-2"><label>2</label><institution>Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China</institution></aff><author-notes><corresp id="CO23110519-1"><bold>Address for correspondence </bold>Riken Chen, MD <institution>Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Guangdong Medical University</institution><addr-line>Zhanjiang, 524003, Guangdong</addr-line><country>China</country><email>chenriken@126.com</email></corresp><corresp id="CO23110519-2">Xishi Sun, MM <institution>Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University</institution><addr-line>Zhanjiang, 524000, Guangdong</addr-line><country>China</country><email>109721368@qq.com</email></corresp></author-notes><pub-date pub-type="epub"><day>23</day><month>5</month><year>2024</year></pub-date><pub-date pub-type="collection"><month>11</month><year>2024</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>5</month><year>2024</year></pub-date><volume>124</volume><issue>11</issue><fpage>1061</fpage><lpage>1074</lpage><history><date date-type="received"><day>27</day><month>11</month><year>2023</year></date><date date-type="accepted"><day>11</day><month>4</month><year>2024</year></date></history><permissions><copyright-statement>
The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (
<uri xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://creativecommons.org/licenses/by-nc-nd/4.0/">https://creativecommons.org/licenses/by-nc-nd/4.0/</uri>
)
</copyright-statement><copyright-year>2024</copyright-year><copyright-holder>The Author(s).</copyright-holder><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/" specific-use="textmining" content-type="ccbyncndlicense">https://creativecommons.org/licenses/by-nc-nd/4.0/</ali:license_ref><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited.</license-p></license></permissions><abstract abstract-type="graphical"><p><bold>Background</bold>
&#x02003;Despite previous observational studies linking obstructive sleep apnea (OSA) to venous thromboembolism (VTE), these findings remain controversial. This study aimed to explore the association between OSA and VTE, including pulmonary embolism (PE) and deep vein thrombosis (DVT), at a genetic level using a bidirectional two-sample Mendelian randomization (MR) analysis.
</p><p><bold>Methods</bold>
&#x02003;Utilizing summary-level data from large-scale genome-wide association studies in European individuals, we designed a bidirectional two-sample MR analysis to comprehensively assess the genetic association between OSA and VTE. The inverse variance weighted was used as the primary method for MR analysis. In addition, MR&#x02013;Egger, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for complementary analyses. Furthermore, a series of sensitivity analyses were performed to ensure the validity and robustness of the results.
</p><p><bold>Results</bold>
&#x02003;The initial and validation MR analyses indicated that genetically predicted OSA had no effects on the risk of VTE (including PE and DVT). Likewise, the reverse MR analysis did not find substantial support for a significant association between VTE (including PE and DVT) and OSA. Supplementary MR methods and sensitivity analyses provided additional confirmation of the reliability of the MR results.
</p><p><bold>Conclusion</bold>
&#x02003;Our bidirectional two-sample MR analysis did not find genetic evidence supporting a significant association between OSA and VTE in either direction.
</p><graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="10-1055-a-2308-2290-i23110519-toc.jpg"/></abstract><kwd-group><title>Keywords</title><kwd>obstructive sleep apnea</kwd><kwd>venous thromboembolism</kwd><kwd>Mendelian randomization</kwd><kwd>association</kwd></kwd-group><funding-group><funding-statement><bold>Funding</bold>
This study was supported by the High-level Talents Scientific Research Start-up Funds of the Affiliated Hospital of Guangdong Medical University (GCC2022028), the Health Development Promotion Project-Anesthesia and Critical Care Research Project (KM-20231120-01), Guangdong Medical Research Fund Project (A2024728, A2024723), Zhanjiang Science and Technology Research Project in 2022 (No: 2022A01197), and the Science and Technology Development Special Fund Competitive Allocation Project of Zhanjiang City (No: 2021A05086).
</funding-statement></funding-group></article-meta></front><body><sec><title>Introduction</title><p>
Obstructive sleep apnea (OSA) is a prevalent sleep disorder characterized by the recurrent partial or complete obstruction and collapse of the upper airway during sleep, leading to episodes of apneas and hypoventilation.
<xref rid="JR23110519-1" ref-type="bibr">1</xref>
<xref rid="JR23110519-2" ref-type="bibr">2</xref>
Research studies have reported that the prevalence of OSA in the adult population ranges from 9 to 38%, with a higher prevalence observed in males (13&#x02013;33%) compared to females (6&#x02013;19%). Moreover, the prevalence of OSA tends to increase with age and is closely associated with the prevalence of obesity.
<xref rid="JR23110519-3" ref-type="bibr">3</xref>
<xref rid="JR23110519-4" ref-type="bibr">4</xref>
</p><p>
There is mounting evidence indicating that OSA serves as an independent risk factor for several cardiovascular diseases, including hypertension,
<xref rid="JR23110519-5" ref-type="bibr">5</xref>
stroke,
<xref rid="JR23110519-6" ref-type="bibr">6</xref>
pulmonary hypertension,
<xref rid="JR23110519-7" ref-type="bibr">7</xref>
and heart failure.
<xref rid="JR23110519-8" ref-type="bibr">8</xref>
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is recognized as the third most common cardiovascular disease worldwide.
<xref rid="JR23110519-9" ref-type="bibr">9</xref>
There is evidence suggesting that OSA may also be linked to an increased risk of VTE.
<xref rid="JR23110519-10" ref-type="bibr">10</xref>
For instance, a prospective study involving 15,664 subjects (1,424 subjects with OSA) observed a twofold higher incidence of VTE in patients with OSA compared to non-OSA patients.
<xref rid="JR23110519-11" ref-type="bibr">11</xref>
Similarly, findings from a national retrospective cohort study conducted by Peng and his colleagues indicated that patients with OSA had a 3.50-fold higher risk of DVT and a 3.97-fold higher risk of PE compared to the general population.
<xref rid="JR23110519-12" ref-type="bibr">12</xref>
However, the results of observational studies remain somewhat controversial. A 5-year prospective study involving 2,109 subjects concluded that OSA did not increase the risk of VTE recurrence.
<xref rid="JR23110519-13" ref-type="bibr">13</xref>
Another retrospective analysis involving 1,584 patients, of which 848 were women, revealed an intriguing discovery suggesting that OSA may serve as an independent risk factor for VTE solely in women, rather than in men.
<xref rid="JR23110519-14" ref-type="bibr">14</xref>
Moreover, patients with VTE were found to have a higher prevalence of OSA,
<xref rid="JR23110519-15" ref-type="bibr">15</xref>
suggesting a potential bidirectional relationship.
</p><p>
Although previous observational studies have investigated the potential association between OSA and VTE, elucidating aspects of the association from these studies is challenging due to the limitations of potential confounders and reverse causality bias. Mendelian randomization (MR) is a genetic epidemiological methodology that utilizes genetic variants, such as single-nucleotide polymorphisms (SNPs), as instrumental variables (IVs) to infer the genetic association between exposure and outcome.
<xref rid="JR23110519-16" ref-type="bibr">16</xref>
The advantage of MR analysis lies in the random assignment of genetic variants during meiosis, which effectively circumvents the effects of potential confounders and reverse causality encountered in classical epidemiologic studies.
<xref rid="JR23110519-17" ref-type="bibr">17</xref>
</p><p>At present, the nature of the association between OSA and VTE remains inconclusive, and there is a dearth of pertinent studies comprehensively exploring the genetic association between OSA and VTE. Therefore, this study aimed to conduct a bidirectional two-sample MR analysis using publicly available summary statistics from large-scale genome-wide association studies (GWAS) to genetically assess the exact association between OSA and VTE, including PE and DVT.</p></sec><sec><title>Methods</title><sec><title>Study Design</title><p>MR utilizes genetic variants, primarily SNPs, as IVs to investigate the genetic association between exposure and outcome. MR is based on three fundamental assumptions: (1) genetic variants exhibit a high correlation with exposure; (2) genetic variants are independent of potential confounders; (3) genetic variants solely affect outcomes through exposure. IVs are deemed valid only when these assumptions are met.</p><p>This study employed a bidirectional two-sample MR analysis to evaluate the genetic association between OSA and VTE. Initially, SNPs associated with OSA were utilized to examine their effects on VTE. Subsequently, to investigate the possibility of reverse association, eligible IVs were employed to quantify the implications of VTE on OSA.</p></sec><sec><title>Data Source and Selection of Instrumental Variables</title><p>OSA was defined based on subjective symptoms, clinical examination, and sleep registration applying apnea&#x02013;hypopnea index &#x02265;5/hour or respiratory event index &#x02265;5/hour.</p><p>
Summary-level data for OSA were obtained from the GWAS study conducted by Jiang et al on European individuals, which included 2,827 cases and 453,521 controls, covering 11,831,932 SNPs.
<xref rid="JR23110519-18" ref-type="bibr">18</xref>
To ensure the robustness of the findings, additional datasets for OSA were acquired from a GWAS meta-analysis conducted by Campos and colleagues, comprising 25,008 cases of European ancestry and 337,630 controls, involving 9,031,949 SNPs for validation analysis.
<xref rid="JR23110519-19" ref-type="bibr">19</xref>
The study conducted a meta-analysis of GWAS datasets from five cohorts in the United Kingdom, Canada, Australia, the United States, and Finland. These summary-level GWAS statistics for OSA can be accessed from the GWAS Catalog (
<uri xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://www.ebi.ac.uk/gwas/downloads">https://www.ebi.ac.uk/gwas/downloads</uri>
). VTE was defined as a condition comprising PE (blockage of the pulmonary artery or its branches by an embolus) and DVT (formation of a blood clot in a deep vein). The GWAS datasets for VTE (19,372 cases and 357,905 controls), PE (9,243 cases and 367,108 controls), and DVT (9,109 cases and 324,121 controls) were derived from the FinnGen consortium (Release 9,
<uri xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://r9.finngen.fi/">https://r9.finngen.fi/</uri>
). Detailed information regarding the data sources is provided in
<xref rid="TB23110519-1" ref-type="table">Table 1</xref>
.
</p><table-wrap id="TB23110519-1"><label>Table 1</label><caption><title>Information on data sources</title></caption><table rules="all"><colgroup align="left" span="7"><col align="left" width="61.4pt"/><col align="left" width="41.3pt"/><col align="left" width="27.3pt"/><col align="left" width="31.8pt"/><col align="left" width="39.3pt"/><col align="left" width="57.8pt"/><col align="left" width="82.3pt"/></colgroup><thead><tr><th align="left" valign="bottom">Trait</th><th align="left" valign="bottom">Sample size</th><th align="left" valign="bottom">Case</th><th align="left" valign="bottom">Control</th><th align="left" valign="bottom">No. of SNPs</th><th align="left" valign="bottom">Participates</th><th align="left" valign="bottom">PMID/Link</th></tr></thead><tbody><tr><td align="left" valign="top">OSA (Jiang et al)</td><td align="left" valign="top">456,348</td><td align="left" valign="top">2,827</td><td align="left" valign="top">453,521</td><td align="left" valign="top">11,831,932</td><td align="left" valign="top">European ancestry</td><td align="left" valign="top">34737426</td></tr><tr><td align="left" valign="top">OSA (Campos et al)</td><td align="left" valign="top">362,638</td><td align="left" valign="top">25,008</td><td align="left" valign="top">337,630</td><td align="left" valign="top">9,031,949</td><td align="left" valign="top">European ancestry</td><td align="left" valign="top">36525587</td></tr><tr><td align="left" valign="top">VTE</td><td align="left" valign="top">377,277</td><td align="left" valign="top">19,372</td><td align="left" valign="top">357,905</td><td align="left" valign="top">20,170,236</td><td align="left" valign="top">European ancestry</td><td align="left" valign="top">
FinnGen consortium (
<uri xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://www.finngen.fi/fi">https://www.finngen.fi/fi</uri>
)
</td></tr><tr><td align="left" valign="top">PE</td><td align="left" valign="top">376,351</td><td align="left" valign="top">9,243</td><td align="left" valign="top">367,108</td><td align="left" valign="top">20,170,202</td><td align="left" valign="top">European ancestry</td><td align="left" valign="top">
FinnGen consortium (
<uri xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://www.finngen.fi/fi">https://www.finngen.fi/fi</uri>
)
</td></tr><tr><td align="left" valign="top">DVT</td><td align="left" valign="top">333,230</td><td align="left" valign="top">9,109</td><td align="left" valign="top">324,121</td><td align="left" valign="top">20,169,198</td><td align="left" valign="top">European ancestry</td><td align="left" valign="top">
FinnGen consortium (
<uri xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://www.finngen.fi/fi">https://www.finngen.fi/fi</uri>
)
</td></tr></tbody></table><table-wrap-foot><fn id="FN23110519-2"><p>Abbreviations: DVT, deep vein thrombosis; OSA, obstructive sleep apnea; PE, pulmonary embolism; SNPs, single-nucleotide polymorphisms; VTE, venous thromboembolism.</p></fn></table-wrap-foot></table-wrap><p>
The selection criteria for IVs were as follows: (1) the threshold for genome-wide significant SNPs for VTE (including PE and DVT) was set at
<italic>p</italic>
&#x02009;&#x0003c;&#x02009;5.0&#x02009;&#x000d7;&#x02009;10
<sup>&#x02212;8</sup>
, while the threshold for OSA was adjusted to
<italic>p</italic>
&#x02009;&#x0003c;&#x02009;1&#x02009;&#x000d7;&#x02009;10
<sup>&#x02212;5</sup>
due to the inability to detect OSA-associated SNPs using a significance level of
<italic>p</italic>
&#x02009;&#x0003c;&#x02009;5.0&#x02009;&#x000d7;&#x02009;10
<sup>&#x02212;8</sup>
. (2) SNPs with linkage disequilibrium effects (
<italic>r</italic>
<sup>2</sup>
&#x02009;&#x0003c;&#x02009;0.001 within a 10,000-kb window) were excluded to ensure the independence of the selected IVs. (3) The strength of the association between IVs and exposure was measured using the F-statistic [F-statistic&#x02009;=&#x02009;(Beta/SE)
<sup>2</sup>
].
<xref rid="JR23110519-20" ref-type="bibr">20</xref>
SNPs with F-statistics &#x0003e;10 were retained to avoid the effects of weak instrumental bias. (4) During the harmonization process, SNPs that did not match the results were removed, along with palindromic SNPs with ambiguous allele frequencies (0.42&#x02013;0.58).
<xref rid="JR23110519-21" ref-type="bibr">21</xref>
(5) Previous studies have demonstrated obesity as an established risk factor for OSA and VTE.
<xref rid="JR23110519-22" ref-type="bibr">22</xref>
<xref rid="JR23110519-23" ref-type="bibr">23</xref>
SNPs associated with body mass index were queried and excluded by Phenoscanner (http://www.phenoscanner.medschl.cam.ac.uk/). The flowchart of IV selection is shown in
<xref rid="FI23110519-1" ref-type="fig">Fig. 1</xref>
.
</p><fig id="FI23110519-1"><label>Fig. 1</label><caption><p>
The flowchart of instrumental variables selection. LD, linkage disequilibrium; SNPs, single-nucleotide polymorphisms; BMI, body mass index; VTE, venous thromboembolism; PE, pulmonary embolism; DVT, deep vein thrombosis; OSA, obstructive sleep apnea; &#x02460;, represents OSA (Jiang et al) as the outcome; &#x02461;, represents OSA (Campos et al) as the outcome.
</p></caption><graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="10-1055-a-2308-2290-i23110519-1"/></fig></sec><sec><title>Statistical Analysis</title><p>
This study employed the multiplicative random-effects inverse variance weighted (IVW) method as the primary approach for conducting MR analysis to evaluate the genetic association between OSA and VTE. The IVW method meta-analyzes the Wald ratio estimates for each SNP on the outcome, providing precise estimates of causal effects when all selected SNPs are valid IVs.
<xref rid="JR23110519-24" ref-type="bibr">24</xref>
However, the estimates of causal effects from the IVW method may be biased by the influence of pleiotropic IVs. To ensure the validity and robustness of the results, sensitivity analyses were implemented using three additional MR methods, namely MR&#x02013;Egger, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO). The MR&#x02013;Egger method is able to generate reliable causal estimates even in situations where all IVs are invalid. Additionally, MR&#x02013;Egger offers an intercept test to detect horizontal pleiotropy, with a significance threshold of
<italic>p</italic>
&#x0003c;0.05 indicating the presence of horizontal pleiotropy.
<xref rid="JR23110519-25" ref-type="bibr">25</xref>
In comparison to the IVW and MR&#x02013;Egger methods, the weighted median method demonstrates greater robustness and provides consistent estimates of causal effects, even when up to 50% of the IVs are invalid instruments.
<xref rid="JR23110519-26" ref-type="bibr">26</xref>
The MR-PRESSO method identifies outliers with potential horizontal pleiotropy and provides estimates after removing the outliers, where
<italic>p</italic>
&#x0003c;0.05 for the global test indicates the presence of outliers with horizontal pleiotropy.
<xref rid="JR23110519-27" ref-type="bibr">27</xref>
Furthermore, the Cochran Q test was utilized to examine heterogeneity, with a significance threshold of
<italic>p</italic>
&#x0003c;0.05 indicating significant heterogeneity.
</p><p>All statistical analyses were carried out using the &#x0201c;TwoSampleMR&#x0201d; and &#x0201c;MRPRESSO&#x0201d; packages in R software (version 4.2.1).</p></sec></sec><sec><title>Results</title><sec><title>Instrumental Variable Selection</title><p>
As previously outlined, a total of 13 and 28 SNPs were identified through a rigorous screening process to evaluate the effects of OSA on VTE, PE, and DVT. In the reverse MR analysis, 23, 14, 18, 19, 11, and 13 SNPs were identified to assess the implications of reverse association, respectively. Additional details regarding these genetic variants utilized for MR analysis are provided in
<xref rid="TB23110519-2" ref-type="table">Tables 2</xref>
and
<xref rid="TB23110519-3" ref-type="table">3</xref>
.
</p><table-wrap id="TB23110519-2"><label>Table 2</label><caption><title>Genetic variants used in the MR analysis</title></caption><table rules="all"><colgroup align="left" span="17"><col align="left" width="3.66%"/><col align="left" width="8.14%"/><col align="left" width="3.92%"/><col align="left" width="4.02%"/><col align="left" width="6.02%"/><col align="left" width="6.02%"/><col align="left" width="6.44%"/><col align="left" width="7.08%"/><col align="left" width="6.02%"/><col align="left" width="6.02%"/><col align="left" width="6.02%"/><col align="left" width="6.02%"/><col align="left" width="6.02%"/><col align="left" width="6.02%"/><col align="left" width="6.44%"/><col align="left" width="6.02%"/><col align="left" width="6.02%"/></colgroup><tbody><tr><td align="left" colspan="17" valign="top">
<bold>Genetic instruments for OSA (Jiang et al) and their associations with VTE, PE, and DVT</bold>
</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" colspan="4" valign="top">
<bold>Exposure: OSA (Jiang et al)</bold>
</td><td align="left" colspan="3" valign="top">
<bold>Outcome: VTE</bold>
</td><td align="left" colspan="3" valign="top">
<bold>Outcome: PE</bold>
</td><td align="left" colspan="3" valign="top">
<bold>Outcome: DVT</bold>
</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">
<bold>SNP</bold>
</td><td align="left" valign="top">
<bold>EA</bold>
</td><td align="left" valign="top">
<bold>OA</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td><td align="left" valign="top">
<bold>F-statistic</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td></tr><tr><td align="left" valign="top">1</td><td align="left" valign="top">rs114417992</td><td align="left" valign="top">C</td><td align="left" valign="top">G</td><td align="left" valign="top">0.48798</td><td align="left" valign="top">0.10793</td><td align="left" valign="top">6.15E-06</td><td align="left" valign="top">20.4409</td><td align="left" valign="top">0.00702</td><td align="left" valign="top">0.04378</td><td align="left" valign="top">0.87253</td><td align="left" valign="top">&#x02212;0.0542</td><td align="left" valign="top">0.06211</td><td align="left" valign="top">0.3832</td><td align="left" valign="top">&#x02212;0.0052</td><td align="left" valign="top">0.06334</td><td align="left" valign="top">0.93511</td></tr><tr><td align="left" valign="top">2</td><td align="left" valign="top">rs115071002</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.3775</td><td align="left" valign="top">0.0807</td><td align="left" valign="top">2.90E-06</td><td align="left" valign="top">21.8836</td><td align="left" valign="top">&#x02212;0.0521</td><td align="left" valign="top">0.05045</td><td align="left" valign="top">0.30146</td><td align="left" valign="top">0.0359</td><td align="left" valign="top">0.07185</td><td align="left" valign="top">0.61729</td><td align="left" valign="top">&#x02212;0.0633</td><td align="left" valign="top">0.07247</td><td align="left" valign="top">0.38241</td></tr><tr><td align="left" valign="top">3</td><td align="left" valign="top">rs117025138</td><td align="left" valign="top">C</td><td align="left" valign="top">G</td><td align="left" valign="top">0.42795</td><td align="left" valign="top">0.09571</td><td align="left" valign="top">7.78E-06</td><td align="left" valign="top">19.9915</td><td align="left" valign="top">&#x02212;0.0149</td><td align="left" valign="top">0.05477</td><td align="left" valign="top">0.78611</td><td align="left" valign="top">0.0087</td><td align="left" valign="top">0.07809</td><td align="left" valign="top">0.91129</td><td align="left" valign="top">&#x02212;0.0338</td><td align="left" valign="top">0.07836</td><td align="left" valign="top">0.66637</td></tr><tr><td align="left" valign="top">4</td><td align="left" valign="top">rs117474005</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.64176</td><td align="left" valign="top">0.14138</td><td align="left" valign="top">5.64E-06</td><td align="left" valign="top">20.6051</td><td align="left" valign="top">&#x02212;0.0095</td><td align="left" valign="top">0.04108</td><td align="left" valign="top">0.81724</td><td align="left" valign="top">&#x02212;0.0009</td><td align="left" valign="top">0.05862</td><td align="left" valign="top">0.98772</td><td align="left" valign="top">&#x02212;0.0301</td><td align="left" valign="top">0.05891</td><td align="left" valign="top">0.60971</td></tr><tr><td align="left" valign="top">5</td><td align="left" valign="top">rs139183760</td><td align="left" valign="top">C</td><td align="left" valign="top">G</td><td align="left" valign="top">0.82973</td><td align="left" valign="top">0.16928</td><td align="left" valign="top">9.50E-07</td><td align="left" valign="top">24.0262</td><td align="left" valign="top">0.06514</td><td align="left" valign="top">0.07681</td><td align="left" valign="top">0.39643</td><td align="left" valign="top">0.04441</td><td align="left" valign="top">0.10929</td><td align="left" valign="top">0.68448</td><td align="left" valign="top">0.04761</td><td align="left" valign="top">0.11024</td><td align="left" valign="top">0.66585</td></tr><tr><td align="left" valign="top">6</td><td align="left" valign="top">rs148047757</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.47481</td><td align="left" valign="top">0.10699</td><td align="left" valign="top">9.08E-06</td><td align="left" valign="top">19.6952</td><td align="left" valign="top">&#x02212;0.0522</td><td align="left" valign="top">0.0352</td><td align="left" valign="top">0.13769</td><td align="left" valign="top">&#x02212;0.044</td><td align="left" valign="top">0.04999</td><td align="left" valign="top">0.37895</td><td align="left" valign="top">&#x02212;0.0294</td><td align="left" valign="top">0.05078</td><td align="left" valign="top">0.562</td></tr><tr><td align="left" valign="top">7</td><td align="left" valign="top">rs150798389</td><td align="left" valign="top">C</td><td align="left" valign="top">A</td><td align="left" valign="top">0.7875</td><td align="left" valign="top">0.17391</td><td align="left" valign="top">5.95E-06</td><td align="left" valign="top">20.505</td><td align="left" valign="top">&#x02212;0.2884</td><td align="left" valign="top">0.1435</td><td align="left" valign="top">0.04447</td><td align="left" valign="top">&#x02212;0.2436</td><td align="left" valign="top">0.20053</td><td align="left" valign="top">0.22438</td><td align="left" valign="top">&#x02212;0.1329</td><td align="left" valign="top">0.20679</td><td align="left" valign="top">0.52056</td></tr><tr><td align="left" valign="top">8</td><td align="left" valign="top">rs16850412</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.19514</td><td align="left" valign="top">0.04353</td><td align="left" valign="top">7.36E-06</td><td align="left" valign="top">20.0977</td><td align="left" valign="top">0.02674</td><td align="left" valign="top">0.01584</td><td align="left" valign="top">0.09145</td><td align="left" valign="top">0.04785</td><td align="left" valign="top">0.02253</td><td align="left" valign="top">0.03368</td><td align="left" valign="top">0.0173</td><td align="left" valign="top">0.02277</td><td align="left" valign="top">0.44739</td></tr><tr><td align="left" valign="top">9</td><td align="left" valign="top">rs1911999</td><td align="left" valign="top">C</td><td align="left" valign="top">T</td><td align="left" valign="top">&#x02212;0.1312</td><td align="left" valign="top">0.02965</td><td align="left" valign="top">9.59E-06</td><td align="left" valign="top">19.5917</td><td align="left" valign="top">0.01759</td><td align="left" valign="top">0.01111</td><td align="left" valign="top">0.11349</td><td align="left" valign="top">0.0376</td><td align="left" valign="top">0.01577</td><td align="left" valign="top">0.01714</td><td align="left" valign="top">0.00223</td><td align="left" valign="top">0.01596</td><td align="left" valign="top">0.88889</td></tr><tr><td align="left" valign="top">10</td><td align="left" valign="top">rs2302012</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.12829</td><td align="left" valign="top">0.02871</td><td align="left" valign="top">7.88E-06</td><td align="left" valign="top">19.9669</td><td align="left" valign="top">&#x02212;0.0104</td><td align="left" valign="top">0.01076</td><td align="left" valign="top">0.33549</td><td align="left" valign="top">&#x02212;0.0272</td><td align="left" valign="top">0.0153</td><td align="left" valign="top">0.07541</td><td align="left" valign="top">0.00767</td><td align="left" valign="top">0.01545</td><td align="left" valign="top">0.61949</td></tr><tr><td align="left" valign="top">11</td><td align="left" valign="top">rs35963104</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.16572</td><td align="left" valign="top">0.03452</td><td align="left" valign="top">1.59E-06</td><td align="left" valign="top">23.0393</td><td align="left" valign="top">&#x02212;0.0076</td><td align="left" valign="top">0.01354</td><td align="left" valign="top">0.57685</td><td align="left" valign="top">&#x02212;0.02</td><td align="left" valign="top">0.01924</td><td align="left" valign="top">0.29896</td><td align="left" valign="top">&#x02212;0.007</td><td align="left" valign="top">0.01942</td><td align="left" valign="top">0.71778</td></tr><tr><td align="left" valign="top">12</td><td align="left" valign="top">rs60445800</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.29191</td><td align="left" valign="top">0.06499</td><td align="left" valign="top">7.06E-06</td><td align="left" valign="top">20.1758</td><td align="left" valign="top">&#x02212;0.0268</td><td align="left" valign="top">0.02361</td><td align="left" valign="top">0.25672</td><td align="left" valign="top">&#x02212;0.0649</td><td align="left" valign="top">0.03349</td><td align="left" valign="top">0.05277</td><td align="left" valign="top">0.0112</td><td align="left" valign="top">0.03388</td><td align="left" valign="top">0.74095</td></tr><tr><td align="left" valign="top">13</td><td align="left" valign="top">rs9587442</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.44308</td><td align="left" valign="top">0.09584</td><td align="left" valign="top">3.78E-06</td><td align="left" valign="top">21.3735</td><td align="left" valign="top">&#x02212;0.0385</td><td align="left" valign="top">0.03346</td><td align="left" valign="top">0.24969</td><td align="left" valign="top">&#x02212;0.0101</td><td align="left" valign="top">0.04781</td><td align="left" valign="top">0.83322</td><td align="left" valign="top">0.00182</td><td align="left" valign="top">0.04783</td><td align="left" valign="top">0.96962</td></tr><tr><td align="left" colspan="17" valign="top">
<bold>Genetic instruments for OSA (Campos et al) and their associations with VTE, PE, and DVT</bold>
</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" colspan="4" valign="top">
<bold>Exposure: OSA (Campos et al)</bold>
</td><td align="left" colspan="3" valign="top">
<bold>Outcome: VTE</bold>
</td><td align="left" colspan="3" valign="top">
<bold>Outcome: PE</bold>
</td><td align="left" colspan="3" valign="top">
<bold>Outcome: DVT</bold>
</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">
<bold>SNP</bold>
</td><td align="left" valign="top">
<bold>EA</bold>
</td><td align="left" valign="top">
<bold>OA</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td><td align="left" valign="top">
<bold>F-statistic</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td></tr><tr><td align="left" valign="top">1</td><td align="left" valign="top">rs10777826</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.0319</td><td align="left" valign="top">0.00664</td><td align="left" valign="top">1.58E-06</td><td align="left" valign="top">23.0496</td><td align="left" valign="top">0.00684</td><td align="left" valign="top">0.01097</td><td align="left" valign="top">0.53296</td><td align="left" valign="top">0.01049</td><td align="left" valign="top">0.01557</td><td align="left" valign="top">0.50053</td><td align="left" valign="top">0.01763</td><td align="left" valign="top">0.01576</td><td align="left" valign="top">0.26318</td></tr><tr><td align="left" valign="top">2</td><td align="left" valign="top">rs10878269</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.03308</td><td align="left" valign="top">0.0069</td><td align="left" valign="top">1.61E-06</td><td align="left" valign="top">23.0112</td><td align="left" valign="top">&#x02212;0.0208</td><td align="left" valign="top">0.01191</td><td align="left" valign="top">0.08097</td><td align="left" valign="top">&#x02212;0.0262</td><td align="left" valign="top">0.01693</td><td align="left" valign="top">0.12108</td><td align="left" valign="top">&#x02212;0.015</td><td align="left" valign="top">0.01711</td><td align="left" valign="top">0.37964</td></tr><tr><td align="left" valign="top">3</td><td align="left" valign="top">rs111909157</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.1355</td><td align="left" valign="top">0.02658</td><td align="left" valign="top">3.40E-07</td><td align="left" valign="top">26.01</td><td align="left" valign="top">0.02664</td><td align="left" valign="top">0.04222</td><td align="left" valign="top">0.52808</td><td align="left" valign="top">0.03995</td><td align="left" valign="top">0.05999</td><td align="left" valign="top">0.5054</td><td align="left" valign="top">0.0364</td><td align="left" valign="top">0.06089</td><td align="left" valign="top">0.55</td></tr><tr><td align="left" valign="top">4</td><td align="left" valign="top">rs116114601</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">&#x02212;0.0873</td><td align="left" valign="top">0.01969</td><td align="left" valign="top">9.20E-06</td><td align="left" valign="top">19.6692</td><td align="left" valign="top">&#x02212;0.0401</td><td align="left" valign="top">0.04098</td><td align="left" valign="top">0.32779</td><td align="left" valign="top">&#x02212;0.0676</td><td align="left" valign="top">0.05814</td><td align="left" valign="top">0.24516</td><td align="left" valign="top">&#x02212;0.0182</td><td align="left" valign="top">0.05873</td><td align="left" valign="top">0.75679</td></tr><tr><td align="left" valign="top">5</td><td align="left" valign="top">rs11989172</td><td align="left" valign="top">C</td><td align="left" valign="top">G</td><td align="left" valign="top">&#x02212;0.0378</td><td align="left" valign="top">0.00839</td><td align="left" valign="top">6.73E-06</td><td align="left" valign="top">20.268</td><td align="left" valign="top">&#x02212;0.0217</td><td align="left" valign="top">0.01283</td><td align="left" valign="top">0.09</td><td align="left" valign="top">&#x02212;0.039</td><td align="left" valign="top">0.01823</td><td align="left" valign="top">0.03222</td><td align="left" valign="top">0.01058</td><td align="left" valign="top">0.01842</td><td align="left" valign="top">0.56561</td></tr><tr><td align="left" valign="top">6</td><td align="left" valign="top">rs12265404</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.04931</td><td align="left" valign="top">0.01041</td><td align="left" valign="top">2.17E-06</td><td align="left" valign="top">22.4392</td><td align="left" valign="top">0.05233</td><td align="left" valign="top">0.0166</td><td align="left" valign="top">0.00162</td><td align="left" valign="top">0.05687</td><td align="left" valign="top">0.0233</td><td align="left" valign="top">0.01467</td><td align="left" valign="top">0.04278</td><td align="left" valign="top">0.02358</td><td align="left" valign="top">0.06956</td></tr><tr><td align="left" valign="top">7</td><td align="left" valign="top">rs12306339</td><td align="left" valign="top">A</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.0488</td><td align="left" valign="top">0.01083</td><td align="left" valign="top">6.64E-06</td><td align="left" valign="top">20.295</td><td align="left" valign="top">&#x02212;0.0051</td><td align="left" valign="top">0.01804</td><td align="left" valign="top">0.77914</td><td align="left" valign="top">&#x02212;0.023</td><td align="left" valign="top">0.02561</td><td align="left" valign="top">0.37006</td><td align="left" valign="top">0.01462</td><td align="left" valign="top">0.02593</td><td align="left" valign="top">0.57292</td></tr><tr><td align="left" valign="top">8</td><td align="left" valign="top">rs13098300</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.03715</td><td align="left" valign="top">0.00712</td><td align="left" valign="top">1.84E-07</td><td align="left" valign="top">27.1962</td><td align="left" valign="top">0.00251</td><td align="left" valign="top">0.01202</td><td align="left" valign="top">0.83434</td><td align="left" valign="top">0.0101</td><td align="left" valign="top">0.01708</td><td align="left" valign="top">0.55432</td><td align="left" valign="top">5.55E-05</td><td align="left" valign="top">0.01727</td><td align="left" valign="top">0.99744</td></tr><tr><td align="left" valign="top">9</td><td align="left" valign="top">rs140548601</td><td align="left" valign="top">C</td><td align="left" valign="top">G</td><td align="left" valign="top">&#x02212;0.1158</td><td align="left" valign="top">0.02428</td><td align="left" valign="top">1.85E-06</td><td align="left" valign="top">22.7529</td><td align="left" valign="top">0.05503</td><td align="left" valign="top">0.04711</td><td align="left" valign="top">0.24277</td><td align="left" valign="top">0.09206</td><td align="left" valign="top">0.06692</td><td align="left" valign="top">0.16895</td><td align="left" valign="top">0.04613</td><td align="left" valign="top">0.06762</td><td align="left" valign="top">0.49515</td></tr><tr><td align="left" valign="top">10</td><td align="left" valign="top">rs143417867</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">&#x02212;0.3666</td><td align="left" valign="top">0.07088</td><td align="left" valign="top">2.30E-07</td><td align="left" valign="top">26.7599</td><td align="left" valign="top">&#x02212;0.1487</td><td align="left" valign="top">0.2216</td><td align="left" valign="top">0.5021</td><td align="left" valign="top">0.15664</td><td align="left" valign="top">0.31582</td><td align="left" valign="top">0.61991</td><td align="left" valign="top">&#x02212;0.0868</td><td align="left" valign="top">0.31594</td><td align="left" valign="top">0.78353</td></tr><tr><td align="left" valign="top">11</td><td align="left" valign="top">rs1942263</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.04569</td><td align="left" valign="top">0.01016</td><td align="left" valign="top">6.93E-06</td><td align="left" valign="top">20.214</td><td align="left" valign="top">&#x02212;0.0156</td><td align="left" valign="top">0.01713</td><td align="left" valign="top">0.36361</td><td align="left" valign="top">&#x02212;0.0136</td><td align="left" valign="top">0.02436</td><td align="left" valign="top">0.57584</td><td align="left" valign="top">&#x02212;0.0318</td><td align="left" valign="top">0.02468</td><td align="left" valign="top">0.19751</td></tr><tr><td align="left" valign="top">12</td><td align="left" valign="top">rs2876633</td><td align="left" valign="top">A</td><td align="left" valign="top">T</td><td align="left" valign="top">&#x02212;0.0355</td><td align="left" valign="top">0.00695</td><td align="left" valign="top">3.43E-07</td><td align="left" valign="top">25.9896</td><td align="left" valign="top">&#x02212;0.0104</td><td align="left" valign="top">0.01158</td><td align="left" valign="top">0.36765</td><td align="left" valign="top">&#x02212;0.0104</td><td align="left" valign="top">0.01645</td><td align="left" valign="top">0.52845</td><td align="left" valign="top">0.0032</td><td align="left" valign="top">0.01664</td><td align="left" valign="top">0.84772</td></tr><tr><td align="left" valign="top">13</td><td align="left" valign="top">rs35847366</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.0545</td><td align="left" valign="top">0.01172</td><td align="left" valign="top">3.31E-06</td><td align="left" valign="top">21.6318</td><td align="left" valign="top">&#x02212;0.0365</td><td align="left" valign="top">0.01831</td><td align="left" valign="top">0.04596</td><td align="left" valign="top">&#x02212;0.0383</td><td align="left" valign="top">0.02603</td><td align="left" valign="top">0.14125</td><td align="left" valign="top">&#x02212;0.0511</td><td align="left" valign="top">0.02629</td><td align="left" valign="top">0.0517</td></tr><tr><td align="left" valign="top">14</td><td align="left" valign="top">rs36051007</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.03481</td><td align="left" valign="top">0.00716</td><td align="left" valign="top">1.14E-06</td><td align="left" valign="top">23.6682</td><td align="left" valign="top">&#x02212;0.0037</td><td align="left" valign="top">0.01095</td><td align="left" valign="top">0.73452</td><td align="left" valign="top">&#x02212;0.0145</td><td align="left" valign="top">0.01557</td><td align="left" valign="top">0.35199</td><td align="left" valign="top">0.00723</td><td align="left" valign="top">0.01573</td><td align="left" valign="top">0.64597</td></tr><tr><td align="left" valign="top">15</td><td align="left" valign="top">rs3774800</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">&#x02212;0.0309</td><td align="left" valign="top">0.0069</td><td align="left" valign="top">7.79E-06</td><td align="left" valign="top">19.9898</td><td align="left" valign="top">0.00395</td><td align="left" valign="top">0.01151</td><td align="left" valign="top">0.73124</td><td align="left" valign="top">&#x02212;0.0107</td><td align="left" valign="top">0.01634</td><td align="left" valign="top">0.51218</td><td align="left" valign="top">0.0093</td><td align="left" valign="top">0.01654</td><td align="left" valign="top">0.57396</td></tr><tr><td align="left" valign="top">16</td><td align="left" valign="top">rs4542364</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.03028</td><td align="left" valign="top">0.00673</td><td align="left" valign="top">6.69E-06</td><td align="left" valign="top">20.277</td><td align="left" valign="top">&#x02212;0.0053</td><td align="left" valign="top">0.01084</td><td align="left" valign="top">0.6236</td><td align="left" valign="top">&#x02212;0.0199</td><td align="left" valign="top">0.01541</td><td align="left" valign="top">0.19737</td><td align="left" valign="top">0.00163</td><td align="left" valign="top">0.01559</td><td align="left" valign="top">0.91663</td></tr><tr><td align="left" valign="top">17</td><td align="left" valign="top">rs4675933</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.0329</td><td align="left" valign="top">0.00709</td><td align="left" valign="top">3.44E-06</td><td align="left" valign="top">21.5482</td><td align="left" valign="top">0.00822</td><td align="left" valign="top">0.01093</td><td align="left" valign="top">0.45187</td><td align="left" valign="top">0.00396</td><td align="left" valign="top">0.01554</td><td align="left" valign="top">0.79863</td><td align="left" valign="top">0.01593</td><td align="left" valign="top">0.01568</td><td align="left" valign="top">0.30957</td></tr><tr><td align="left" valign="top">18</td><td align="left" valign="top">rs533143</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.03237</td><td align="left" valign="top">0.00732</td><td align="left" valign="top">9.73E-06</td><td align="left" valign="top">19.5629</td><td align="left" valign="top">0.02892</td><td align="left" valign="top">0.01429</td><td align="left" valign="top">0.04304</td><td align="left" valign="top">0.02757</td><td align="left" valign="top">0.02031</td><td align="left" valign="top">0.1747</td><td align="left" valign="top">0.0111</td><td align="left" valign="top">0.02054</td><td align="left" valign="top">0.58881</td></tr><tr><td align="left" valign="top">19</td><td align="left" valign="top">rs60653979</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.03384</td><td align="left" valign="top">0.0068</td><td align="left" valign="top">6.43E-07</td><td align="left" valign="top">24.7805</td><td align="left" valign="top">0.01098</td><td align="left" valign="top">0.01083</td><td align="left" valign="top">0.31063</td><td align="left" valign="top">&#x02212;0.0154</td><td align="left" valign="top">0.01539</td><td align="left" valign="top">0.31844</td><td align="left" valign="top">0.02887</td><td align="left" valign="top">0.01557</td><td align="left" valign="top">0.06364</td></tr><tr><td align="left" valign="top">20</td><td align="left" valign="top">rs62559379</td><td align="left" valign="top">C</td><td align="left" valign="top">G</td><td align="left" valign="top">0.0706</td><td align="left" valign="top">0.01455</td><td align="left" valign="top">1.22E-06</td><td align="left" valign="top">23.5419</td><td align="left" valign="top">&#x02212;0.0163</td><td align="left" valign="top">0.02726</td><td align="left" valign="top">0.54934</td><td align="left" valign="top">&#x02212;0.028</td><td align="left" valign="top">0.03871</td><td align="left" valign="top">0.46867</td><td align="left" valign="top">&#x02212;0.0113</td><td align="left" valign="top">0.03915</td><td align="left" valign="top">0.77255</td></tr><tr><td align="left" valign="top">21</td><td align="left" valign="top">rs7106583</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.03868</td><td align="left" valign="top">0.00839</td><td align="left" valign="top">4.09E-06</td><td align="left" valign="top">21.2244</td><td align="left" valign="top">&#x02212;0.0434</td><td align="left" valign="top">0.014</td><td align="left" valign="top">0.00194</td><td align="left" valign="top">&#x02212;0.0205</td><td align="left" valign="top">0.02006</td><td align="left" valign="top">0.30655</td><td align="left" valign="top">&#x02212;0.0414</td><td align="left" valign="top">0.0203</td><td align="left" valign="top">0.04114</td></tr><tr><td align="left" valign="top">22</td><td align="left" valign="top">rs72904209</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.0446</td><td align="left" valign="top">0.00983</td><td align="left" valign="top">5.67E-06</td><td align="left" valign="top">20.5934</td><td align="left" valign="top">&#x02212;0.0153</td><td align="left" valign="top">0.01617</td><td align="left" valign="top">0.34449</td><td align="left" valign="top">&#x02212;0.0355</td><td align="left" valign="top">0.02292</td><td align="left" valign="top">0.1215</td><td align="left" valign="top">&#x02212;0.0066</td><td align="left" valign="top">0.02327</td><td align="left" valign="top">0.77599</td></tr><tr><td align="left" valign="top">23</td><td align="left" valign="top">rs73141516</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.06496</td><td align="left" valign="top">0.01415</td><td align="left" valign="top">4.40E-06</td><td align="left" valign="top">21.0865</td><td align="left" valign="top">0.0084</td><td align="left" valign="top">0.02184</td><td align="left" valign="top">0.70062</td><td align="left" valign="top">&#x02212;0.0241</td><td align="left" valign="top">0.03105</td><td align="left" valign="top">0.43797</td><td align="left" valign="top">0.03405</td><td align="left" valign="top">0.03133</td><td align="left" valign="top">0.27717</td></tr><tr><td align="left" valign="top">24</td><td align="left" valign="top">rs73164714</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.0695</td><td align="left" valign="top">0.01285</td><td align="left" valign="top">6.43E-08</td><td align="left" valign="top">29.2248</td><td align="left" valign="top">&#x02212;0.028</td><td align="left" valign="top">0.03721</td><td align="left" valign="top">0.45256</td><td align="left" valign="top">0.00562</td><td align="left" valign="top">0.05276</td><td align="left" valign="top">0.91513</td><td align="left" valign="top">&#x02212;0.0139</td><td align="left" valign="top">0.05319</td><td align="left" valign="top">0.79352</td></tr><tr><td align="left" valign="top">25</td><td align="left" valign="top">rs7800775</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.03487</td><td align="left" valign="top">0.00785</td><td align="left" valign="top">8.98E-06</td><td align="left" valign="top">19.7136</td><td align="left" valign="top">0.00351</td><td align="left" valign="top">0.01357</td><td align="left" valign="top">0.79598</td><td align="left" valign="top">0.00758</td><td align="left" valign="top">0.01929</td><td align="left" valign="top">0.69414</td><td align="left" valign="top">&#x02212;0.0166</td><td align="left" valign="top">0.01948</td><td align="left" valign="top">0.39528</td></tr><tr><td align="left" valign="top">26</td><td align="left" valign="top">rs794999</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.03421</td><td align="left" valign="top">0.00764</td><td align="left" valign="top">7.64E-06</td><td align="left" valign="top">20.0256</td><td align="left" valign="top">0.00108</td><td align="left" valign="top">0.01258</td><td align="left" valign="top">0.93171</td><td align="left" valign="top">0.0139</td><td align="left" valign="top">0.01786</td><td align="left" valign="top">0.43649</td><td align="left" valign="top">0.00374</td><td align="left" valign="top">0.01807</td><td align="left" valign="top">0.83582</td></tr><tr><td align="left" valign="top">27</td><td align="left" valign="top">rs9464135</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">&#x02212;0.0309</td><td align="left" valign="top">0.00663</td><td align="left" valign="top">3.11E-06</td><td align="left" valign="top">21.7436</td><td align="left" valign="top">&#x02212;0.0076</td><td align="left" valign="top">0.01055</td><td align="left" valign="top">0.47151</td><td align="left" valign="top">0.01164</td><td align="left" valign="top">0.015</td><td align="left" valign="top">0.43786</td><td align="left" valign="top">&#x02212;0.0375</td><td align="left" valign="top">0.01516</td><td align="left" valign="top">0.01337</td></tr><tr><td align="left" valign="top">28</td><td align="left" valign="top">rs9567762</td><td align="left" valign="top">A</td><td align="left" valign="top">T</td><td align="left" valign="top">0.03635</td><td align="left" valign="top">0.00823</td><td align="left" valign="top">9.92E-06</td><td align="left" valign="top">19.5276</td><td align="left" valign="top">0.01223</td><td align="left" valign="top">0.01084</td><td align="left" valign="top">0.25934</td><td align="left" valign="top">0.00403</td><td align="left" valign="top">0.0154</td><td align="left" valign="top">0.7934</td><td align="left" valign="top">0.01552</td><td align="left" valign="top">0.01557</td><td align="left" valign="top">0.31884</td></tr></tbody></table><table-wrap-foot><fn id="FN23110519-3"><p>Abbreviations: DVT, deep vein thrombosis; EA, effect allele; MR, Mendelian randomization; OA, other allele; OSA, obstructive sleep apnea; PE, pulmonary embolism; SE, standard error; SNP, single-nucleotide polymorphism; VTE, venous thromboembolism.</p></fn><fn id="FN23110519-4"><p>
Note: F-statistic&#x02009;=&#x02009;(Beta/SE)
<sup>2</sup>
, represents the strength of each instrumental variable
</p></fn></table-wrap-foot></table-wrap><table-wrap id="TB23110519-3"><label>Table 3</label><caption><title>Genetic variants used in the reverse MR analysis</title></caption><table rules="all"><colgroup align="left" span="11"><col align="left" width="4.42%"/><col align="left" width="12.18%"/><col align="left" width="4.88%"/><col align="left" width="5.06%"/><col align="left" width="10.9%"/><col align="left" width="10.36%"/><col align="left" width="10.18%"/><col align="left" width="10.36%"/><col align="left" width="10.9%"/><col align="left" width="10.36%"/><col align="left" width="10.36%"/></colgroup><tbody><tr><td align="left" colspan="11" valign="top">
<bold>Genetic instruments for VTE/PE/DVT and their associations with OSA (Jiang et al)</bold>
</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" colspan="4" valign="top">
<bold>Exposure: VTE</bold>
</td><td align="left" colspan="3" valign="top">
<bold>Outcome: OSA (Jiang et al)</bold>
</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">
<bold>SNP</bold>
</td><td align="left" valign="top">
<bold>EA</bold>
</td><td align="left" valign="top">
<bold>OA</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td><td align="left" valign="top">
<bold>F-statistic</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td></tr><tr><td align="left" valign="top">1</td><td align="left" valign="top">rs10896706</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.0702142</td><td align="left" valign="top">0.0121006</td><td align="left" valign="top">6.53E-09</td><td align="left" valign="top">33.669456</td><td align="left" valign="top">&#x02212;0.0597845</td><td align="left" valign="top">0.029345</td><td align="left" valign="top">0.0416207</td></tr><tr><td align="left" valign="top">2</td><td align="left" valign="top">rs113079063</td><td align="left" valign="top">T</td><td align="left" valign="top">G</td><td align="left" valign="top">0.378107</td><td align="left" valign="top">0.0507769</td><td align="left" valign="top">9.59E-14</td><td align="left" valign="top">55.449428</td><td align="left" valign="top">0.0050364</td><td align="left" valign="top">0.0876134</td><td align="left" valign="top">0.954159</td></tr><tr><td align="left" valign="top">3</td><td align="left" valign="top">rs114026832</td><td align="left" valign="top">A</td><td align="left" valign="top">C</td><td align="left" valign="top">0.773925</td><td align="left" valign="top">0.099915</td><td align="left" valign="top">9.50E-15</td><td align="left" valign="top">59.997944</td><td align="left" valign="top">0.0578773</td><td align="left" valign="top">0.180543</td><td align="left" valign="top">0.748533</td></tr><tr><td align="left" valign="top">4</td><td align="left" valign="top">rs114767153</td><td align="left" valign="top">T</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.20888</td><td align="left" valign="top">0.0348173</td><td align="left" valign="top">1.98E-09</td><td align="left" valign="top">35.991798</td><td align="left" valign="top">&#x02212;0.0712189</td><td align="left" valign="top">0.0909972</td><td align="left" valign="top">0.433833</td></tr><tr><td align="left" valign="top">5</td><td align="left" valign="top">rs116997538</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.403288</td><td align="left" valign="top">0.0383066</td><td align="left" valign="top">6.42E-26</td><td align="left" valign="top">110.83665</td><td align="left" valign="top">&#x02212;0.067735</td><td align="left" valign="top">0.123897</td><td align="left" valign="top">0.584581</td></tr><tr><td align="left" valign="top">6</td><td align="left" valign="top">rs12054563</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.126677</td><td align="left" valign="top">0.0176431</td><td align="left" valign="top">6.97E-13</td><td align="left" valign="top">51.552027</td><td align="left" valign="top">0.0602695</td><td align="left" valign="top">0.0663601</td><td align="left" valign="top">0.363763</td></tr><tr><td align="left" valign="top">7</td><td align="left" valign="top">rs1560711</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.122379</td><td align="left" valign="top">0.0141465</td><td align="left" valign="top">5.11E-18</td><td align="left" valign="top">74.836901</td><td align="left" valign="top">0.0310044</td><td align="left" valign="top">0.0321024</td><td align="left" valign="top">0.334145</td></tr><tr><td align="left" valign="top">8</td><td align="left" valign="top">rs174529</td><td align="left" valign="top">C</td><td align="left" valign="top">T</td><td align="left" valign="top">&#x02212;0.0686342</td><td align="left" valign="top">0.0107211</td><td align="left" valign="top">1.54E-10</td><td align="left" valign="top">40.982878</td><td align="left" valign="top">&#x02212;0.0053417</td><td align="left" valign="top">0.0276673</td><td align="left" valign="top">0.846904</td></tr><tr><td align="left" valign="top">9</td><td align="left" valign="top">rs188337046</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.16048</td><td align="left" valign="top">0.0250424</td><td align="left" valign="top">1.47E-10</td><td align="left" valign="top">41.066712</td><td align="left" valign="top">0.178311</td><td align="left" valign="top">0.206621</td><td align="left" valign="top">0.388145</td></tr><tr><td align="left" valign="top">10</td><td align="left" valign="top">rs2066865</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.186112</td><td align="left" valign="top">0.0112369</td><td align="left" valign="top">1.30E-61</td><td align="left" valign="top">274.31889</td><td align="left" valign="top">0.0083154</td><td align="left" valign="top">0.0313691</td><td align="left" valign="top">0.790945</td></tr><tr><td align="left" valign="top">11</td><td align="left" valign="top">rs2519785</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.0702991</td><td align="left" valign="top">0.0118882</td><td align="left" valign="top">3.35E-09</td><td align="left" valign="top">34.967721</td><td align="left" valign="top">0.0074319</td><td align="left" valign="top">0.0297183</td><td align="left" valign="top">0.802526</td></tr><tr><td align="left" valign="top">12</td><td align="left" valign="top">rs3756011</td><td align="left" valign="top">A</td><td align="left" valign="top">C</td><td align="left" valign="top">0.192712</td><td align="left" valign="top">0.0105525</td><td align="left" valign="top">1.65E-74</td><td align="left" valign="top">333.50841</td><td align="left" valign="top">&#x02212;0.0026386</td><td align="left" valign="top">0.0272831</td><td align="left" valign="top">0.922956</td></tr><tr><td align="left" valign="top">13</td><td align="left" valign="top">rs57328376</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">0.0697584</td><td align="left" valign="top">0.0109198</td><td align="left" valign="top">1.68E-10</td><td align="left" valign="top">40.809724</td><td align="left" valign="top">&#x02212;0.0101806</td><td align="left" valign="top">0.0290533</td><td align="left" valign="top">0.726031</td></tr><tr><td align="left" valign="top">14</td><td align="left" valign="top">rs576123</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.237396</td><td align="left" valign="top">0.0104973</td><td align="left" valign="top">3.09E-113</td><td align="left" valign="top">511.43633</td><td align="left" valign="top">0.00819</td><td align="left" valign="top">0.0287779</td><td align="left" valign="top">0.775956</td></tr><tr><td align="left" valign="top">15</td><td align="left" valign="top">rs5896</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.109291</td><td align="left" valign="top">0.0125852</td><td align="left" valign="top">3.82E-18</td><td align="left" valign="top">75.413406</td><td align="left" valign="top">0.0614773</td><td align="left" valign="top">0.0388191</td><td align="left" valign="top">0.113265</td></tr><tr><td align="left" valign="top">16</td><td align="left" valign="top">rs6025</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.873415</td><td align="left" valign="top">0.0298388</td><td align="left" valign="top">2.42E-188</td><td align="left" valign="top">856.79828</td><td align="left" valign="top">0.0502217</td><td align="left" valign="top">0.0899796</td><td align="left" valign="top">0.576745</td></tr><tr><td align="left" valign="top">17</td><td align="left" valign="top">rs6060308</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.101587</td><td align="left" valign="top">0.0112359</td><td align="left" valign="top">1.55E-19</td><td align="left" valign="top">81.744876</td><td align="left" valign="top">0.0521936</td><td align="left" valign="top">0.0308737</td><td align="left" valign="top">0.0909227</td></tr><tr><td align="left" valign="top">18</td><td align="left" valign="top">rs60681578</td><td align="left" valign="top">C</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.118392</td><td align="left" valign="top">0.0150029</td><td align="left" valign="top">2.99E-15</td><td align="left" valign="top">62.272211</td><td align="left" valign="top">0.0169103</td><td align="left" valign="top">0.0390773</td><td align="left" valign="top">0.665204</td></tr><tr><td align="left" valign="top">19</td><td align="left" valign="top">rs62350309</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.173509</td><td align="left" valign="top">0.0181448</td><td align="left" valign="top">1.15E-21</td><td align="left" valign="top">91.440721</td><td align="left" valign="top">&#x02212;0.071956</td><td align="left" valign="top">0.0634685</td><td align="left" valign="top">0.256909</td></tr><tr><td align="left" valign="top">20</td><td align="left" valign="top">rs628094</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.0818781</td><td align="left" valign="top">0.0114389</td><td align="left" valign="top">8.19E-13</td><td align="left" valign="top">51.235029</td><td align="left" valign="top">0.0027028</td><td align="left" valign="top">0.0302168</td><td align="left" valign="top">0.928726</td></tr><tr><td align="left" valign="top">21</td><td align="left" valign="top">rs72708961</td><td align="left" valign="top">C</td><td align="left" valign="top">T</td><td align="left" valign="top">0.0891913</td><td align="left" valign="top">0.0159445</td><td align="left" valign="top">2.22E-08</td><td align="left" valign="top">31.291269</td><td align="left" valign="top">&#x02212;0.0765307</td><td align="left" valign="top">0.0367798</td><td align="left" valign="top">0.0374539</td></tr><tr><td align="left" valign="top">22</td><td align="left" valign="top">rs7772305</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.0726964</td><td align="left" valign="top">0.0111586</td><td align="left" valign="top">7.28E-11</td><td align="left" valign="top">42.443031</td><td align="left" valign="top">0.0585778</td><td align="left" valign="top">0.0307164</td><td align="left" valign="top">0.0565137</td></tr><tr><td align="left" valign="top">23</td><td align="left" valign="top">rs78807356</td><td align="left" valign="top">T</td><td align="left" valign="top">G</td><td align="left" valign="top">0.541094</td><td align="left" valign="top">0.0563616</td><td align="left" valign="top">7.96E-22</td><td align="left" valign="top">92.167713</td><td align="left" valign="top">0.101617</td><td align="left" valign="top">0.0796139</td><td align="left" valign="top">0.201825</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" colspan="4" valign="top">
<bold>Exposure: PE</bold>
</td><td align="left" colspan="3" valign="top">
<bold>Outcome: OSA (Jiang et al)</bold>
</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">
<bold>SNP</bold>
</td><td align="left" valign="top">
<bold>EA</bold>
</td><td align="left" valign="top">
<bold>OA</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td><td align="left" valign="top">
<bold>F-statistic</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td></tr><tr><td align="left" valign="top">1</td><td align="left" valign="top">rs117210485</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.150787</td><td align="left" valign="top">0.0228699</td><td align="left" valign="top">4.30E-11</td><td align="left" valign="top">43.470964</td><td align="left" valign="top">0.0214618</td><td align="left" valign="top">0.114177</td><td align="left" valign="top">0.8509</td></tr><tr><td align="left" valign="top">2</td><td align="left" valign="top">rs11758950</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.203947</td><td align="left" valign="top">0.0367907</td><td align="left" valign="top">2.97E-08</td><td align="left" valign="top">30.729716</td><td align="left" valign="top">0.0418521</td><td align="left" valign="top">0.0821953</td><td align="left" valign="top">0.610627</td></tr><tr><td align="left" valign="top">3</td><td align="left" valign="top">rs143620474</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.281243</td><td align="left" valign="top">0.0512263</td><td align="left" valign="top">4.01E-08</td><td align="left" valign="top">30.142375</td><td align="left" valign="top">0.546819</td><td align="left" valign="top">0.155226</td><td align="left" valign="top">0.0004271</td></tr><tr><td align="left" valign="top">4</td><td align="left" valign="top">rs1481808</td><td align="left" valign="top">C</td><td align="left" valign="top">T</td><td align="left" valign="top">&#x02212;0.480929</td><td align="left" valign="top">0.0875759</td><td align="left" valign="top">3.98E-08</td><td align="left" valign="top">30.157318</td><td align="left" valign="top">&#x02212;0.164933</td><td align="left" valign="top">0.105459</td><td align="left" valign="top">0.117828</td></tr><tr><td align="left" valign="top">5</td><td align="left" valign="top">rs1560711</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.144704</td><td align="left" valign="top">0.0202073</td><td align="left" valign="top">8.01E-13</td><td align="left" valign="top">51.279584</td><td align="left" valign="top">0.0310044</td><td align="left" valign="top">0.0321024</td><td align="left" valign="top">0.334145</td></tr><tr><td align="left" valign="top">6</td><td align="left" valign="top">rs1894692</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">&#x02212;0.547808</td><td align="left" valign="top">0.0457764</td><td align="left" valign="top">5.29E-33</td><td align="left" valign="top">143.21004</td><td align="left" valign="top">0.0002365</td><td align="left" valign="top">0.0951533</td><td align="left" valign="top">0.998017</td></tr><tr><td align="left" valign="top">7</td><td align="left" valign="top">rs2066865</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.227484</td><td align="left" valign="top">0.0158067</td><td align="left" valign="top">5.85E-47</td><td align="left" valign="top">207.11869</td><td align="left" valign="top">0.0083154</td><td align="left" valign="top">0.0313691</td><td align="left" valign="top">0.790945</td></tr><tr><td align="left" valign="top">8</td><td align="left" valign="top">rs28584824</td><td align="left" valign="top">A</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.155264</td><td align="left" valign="top">0.0279234</td><td align="left" valign="top">2.69E-08</td><td align="left" valign="top">30.917541</td><td align="left" valign="top">&#x02212;0.0268756</td><td align="left" valign="top">0.0782108</td><td align="left" valign="top">0.731124</td></tr><tr><td align="left" valign="top">9</td><td align="left" valign="top">rs3756011</td><td align="left" valign="top">A</td><td align="left" valign="top">C</td><td align="left" valign="top">0.234784</td><td align="left" valign="top">0.0149143</td><td align="left" valign="top">7.77E-56</td><td align="left" valign="top">247.81709</td><td align="left" valign="top">&#x02212;0.0026386</td><td align="left" valign="top">0.0272831</td><td align="left" valign="top">0.922956</td></tr><tr><td align="left" valign="top">10</td><td align="left" valign="top">rs62350309</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.202534</td><td align="left" valign="top">0.0260372</td><td align="left" valign="top">7.33E-15</td><td align="left" valign="top">60.507237</td><td align="left" valign="top">&#x02212;0.071956</td><td align="left" valign="top">0.0634685</td><td align="left" valign="top">0.256909</td></tr><tr><td align="left" valign="top">11</td><td align="left" valign="top">rs635634</td><td align="left" valign="top">C</td><td align="left" valign="top">T</td><td align="left" valign="top">&#x02212;0.239636</td><td align="left" valign="top">0.0177935</td><td align="left" valign="top">2.43E-41</td><td align="left" valign="top">181.37664</td><td align="left" valign="top">0.0064596</td><td align="left" valign="top">0.0347197</td><td align="left" valign="top">0.852404</td></tr><tr><td align="left" valign="top">12</td><td align="left" valign="top">rs665082</td><td align="left" valign="top">C</td><td align="left" valign="top">G</td><td align="left" valign="top">&#x02212;0.175581</td><td align="left" valign="top">0.030484</td><td align="left" valign="top">8.42E-09</td><td align="left" valign="top">33.175015</td><td align="left" valign="top">&#x02212;0.343267</td><td align="left" valign="top">0.216405</td><td align="left" valign="top">0.112688</td></tr><tr><td align="left" valign="top">13</td><td align="left" valign="top">rs77165492</td><td align="left" valign="top">C</td><td align="left" valign="top">T</td><td align="left" valign="top">0.209269</td><td align="left" valign="top">0.0275462</td><td align="left" valign="top">3.03E-14</td><td align="left" valign="top">57.714695</td><td align="left" valign="top">&#x02212;0.0445618</td><td align="left" valign="top">0.0457769</td><td align="left" valign="top">0.330327</td></tr><tr><td align="left" valign="top">14</td><td align="left" valign="top">rs78807356</td><td align="left" valign="top">T</td><td align="left" valign="top">G</td><td align="left" valign="top">0.515784</td><td align="left" valign="top">0.0795096</td><td align="left" valign="top">8.75E-11</td><td align="left" valign="top">42.082022</td><td align="left" valign="top">0.101617</td><td align="left" valign="top">0.0796139</td><td align="left" valign="top">0.201825</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" colspan="4" valign="top">
<bold>Exposure: DVT</bold>
</td><td align="left" colspan="3" valign="top">
<bold>Outcome: OSA (Jiang et al)</bold>
</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">
<bold>SNP</bold>
</td><td align="left" valign="top">
<bold>EA</bold>
</td><td align="left" valign="top">
<bold>OA</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td><td align="left" valign="top">
<bold>F-statistic</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td></tr><tr><td align="left" valign="top">1</td><td align="left" valign="top">rs113079063</td><td align="left" valign="top">T</td><td align="left" valign="top">G</td><td align="left" valign="top">0.436284</td><td align="left" valign="top">0.0717563</td><td align="left" valign="top">1.20E-09</td><td align="left" valign="top">36.967365</td><td align="left" valign="top">0.0050364</td><td align="left" valign="top">0.0876134</td><td align="left" valign="top">0.954159</td></tr><tr><td align="left" valign="top">2</td><td align="left" valign="top">rs116997538</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.466245</td><td align="left" valign="top">0.0534583</td><td align="left" valign="top">2.74E-18</td><td align="left" valign="top">76.067315</td><td align="left" valign="top">&#x02212;0.067735</td><td align="left" valign="top">0.123897</td><td align="left" valign="top">0.584581</td></tr><tr><td align="left" valign="top">3</td><td align="left" valign="top">rs13377102</td><td align="left" valign="top">A</td><td align="left" valign="top">T</td><td align="left" valign="top">&#x02212;0.233255</td><td align="left" valign="top">0.0255094</td><td align="left" valign="top">6.02E-20</td><td align="left" valign="top">83.610619</td><td align="left" valign="top">&#x02212;0.0250186</td><td align="left" valign="top">0.0389518</td><td align="left" valign="top">0.520681</td></tr><tr><td align="left" valign="top">4</td><td align="left" valign="top">rs2066865</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.184507</td><td align="left" valign="top">0.0161145</td><td align="left" valign="top">2.36E-30</td><td align="left" valign="top">131.09678</td><td align="left" valign="top">0.0083154</td><td align="left" valign="top">0.0313691</td><td align="left" valign="top">0.790945</td></tr><tr><td align="left" valign="top">5</td><td align="left" valign="top">rs2289252</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.197972</td><td align="left" valign="top">0.015135</td><td align="left" valign="top">4.26E-39</td><td align="left" valign="top">171.09712</td><td align="left" valign="top">&#x02212;0.0018411</td><td align="left" valign="top">0.0272571</td><td align="left" valign="top">0.946148</td></tr><tr><td align="left" valign="top">6</td><td align="left" valign="top">rs2519785</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.0982467</td><td align="left" valign="top">0.0169973</td><td align="left" valign="top">7.46E-09</td><td align="left" valign="top">33.409968</td><td align="left" valign="top">0.0074319</td><td align="left" valign="top">0.0297183</td><td align="left" valign="top">0.802526</td></tr><tr><td align="left" valign="top">7</td><td align="left" valign="top">rs576123</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.297682</td><td align="left" valign="top">0.014983</td><td align="left" valign="top">7.70E-88</td><td align="left" valign="top">394.73678</td><td align="left" valign="top">0.00819</td><td align="left" valign="top">0.0287779</td><td align="left" valign="top">0.775956</td></tr><tr><td align="left" valign="top">8</td><td align="left" valign="top">rs5896</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.141024</td><td align="left" valign="top">0.017945</td><td align="left" valign="top">3.88E-15</td><td align="left" valign="top">61.75884</td><td align="left" valign="top">0.0614773</td><td align="left" valign="top">0.0388191</td><td align="left" valign="top">0.113265</td></tr><tr><td align="left" valign="top">9</td><td align="left" valign="top">rs6025</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">1.10439</td><td align="left" valign="top">0.0393903</td><td align="left" valign="top">5.71E-173</td><td align="left" valign="top">786.07929</td><td align="left" valign="top">0.0502217</td><td align="left" valign="top">0.0899796</td><td align="left" valign="top">0.576745</td></tr><tr><td align="left" valign="top">10</td><td align="left" valign="top">rs6060237</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">0.168453</td><td align="left" valign="top">0.0198214</td><td align="left" valign="top">1.92E-17</td><td align="left" valign="top">72.225216</td><td align="left" valign="top">0.0318432</td><td align="left" valign="top">0.0414073</td><td align="left" valign="top">0.441879</td></tr><tr><td align="left" valign="top">11</td><td align="left" valign="top">rs60681578</td><td align="left" valign="top">C</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.137615</td><td align="left" valign="top">0.021627</td><td align="left" valign="top">1.98E-10</td><td align="left" valign="top">40.489181</td><td align="left" valign="top">0.0169103</td><td align="left" valign="top">0.0390773</td><td align="left" valign="top">0.665204</td></tr><tr><td align="left" valign="top">12</td><td align="left" valign="top">rs62350309</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.162704</td><td align="left" valign="top">0.0259998</td><td align="left" valign="top">3.90E-10</td><td align="left" valign="top">39.161241</td><td align="left" valign="top">&#x02212;0.071956</td><td align="left" valign="top">0.0634685</td><td align="left" valign="top">0.256909</td></tr><tr><td align="left" valign="top">13</td><td align="left" valign="top">rs666870</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.0924832</td><td align="left" valign="top">0.0159069</td><td align="left" valign="top">6.10E-09</td><td align="left" valign="top">33.802949</td><td align="left" valign="top">0.0127968</td><td align="left" valign="top">0.0271558</td><td align="left" valign="top">0.637472</td></tr><tr><td align="left" valign="top">14</td><td align="left" valign="top">rs7308002</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.0978174</td><td align="left" valign="top">0.01576</td><td align="left" valign="top">5.41E-10</td><td align="left" valign="top">38.522974</td><td align="left" valign="top">&#x02212;0.0027934</td><td align="left" valign="top">0.0275746</td><td align="left" valign="top">0.919309</td></tr><tr><td align="left" valign="top">15</td><td align="left" valign="top">rs76151810</td><td align="left" valign="top">A</td><td align="left" valign="top">C</td><td align="left" valign="top">0.153073</td><td align="left" valign="top">0.0273112</td><td align="left" valign="top">2.09E-08</td><td align="left" valign="top">31.413449</td><td align="left" valign="top">&#x02212;0.0018493</td><td align="left" valign="top">0.0507256</td><td align="left" valign="top">0.970918</td></tr><tr><td align="left" valign="top">16</td><td align="left" valign="top">rs7772305</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.100251</td><td align="left" valign="top">0.016057</td><td align="left" valign="top">4.28E-10</td><td align="left" valign="top">38.980608</td><td align="left" valign="top">0.0585778</td><td align="left" valign="top">0.0307164</td><td align="left" valign="top">0.0565137</td></tr><tr><td align="left" valign="top">17</td><td align="left" valign="top">rs78807356</td><td align="left" valign="top">T</td><td align="left" valign="top">G</td><td align="left" valign="top">0.621447</td><td align="left" valign="top">0.0792414</td><td align="left" valign="top">4.42E-15</td><td align="left" valign="top">61.504078</td><td align="left" valign="top">0.101617</td><td align="left" valign="top">0.0796139</td><td align="left" valign="top">0.201825</td></tr><tr><td align="left" valign="top">18</td><td align="left" valign="top">rs9865118</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.0863804</td><td align="left" valign="top">0.0151814</td><td align="left" valign="top">1.27E-08</td><td align="left" valign="top">32.374776</td><td align="left" valign="top">0.0363583</td><td align="left" valign="top">0.0268338</td><td align="left" valign="top">0.175436</td></tr><tr><td align="left" colspan="11" valign="top">
<bold>Genetic instruments for VTE/PE/DVT and their associations with OSA (Campos et al)</bold>
</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" colspan="4" valign="top">
<bold>Exposure: VTE</bold>
</td><td align="left" colspan="3" valign="top">
<bold>Outcome: OSA (Campos et al)</bold>
</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">
<bold>SNP</bold>
</td><td align="left" valign="top">
<bold>EA</bold>
</td><td align="left" valign="top">
<bold>OA</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td><td align="left" valign="top">
<bold>F-statistic</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td></tr><tr><td align="left" valign="top">1</td><td align="left" valign="top">rs10896706</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.0702142</td><td align="left" valign="top">0.0121006</td><td align="left" valign="top">6.53E-09</td><td align="left" valign="top">33.669456</td><td align="left" valign="top">0.0073376</td><td align="left" valign="top">0.0072794</td><td align="left" valign="top">0.3136</td></tr><tr><td align="left" valign="top">2</td><td align="left" valign="top">rs114767153</td><td align="left" valign="top">T</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.20888</td><td align="left" valign="top">0.0348173</td><td align="left" valign="top">1.98E-09</td><td align="left" valign="top">35.991798</td><td align="left" valign="top">&#x02212;0.0240477</td><td align="left" valign="top">0.0220217</td><td align="left" valign="top">0.2749</td></tr><tr><td align="left" valign="top">3</td><td align="left" valign="top">rs116997538</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.403288</td><td align="left" valign="top">0.0383066</td><td align="left" valign="top">6.42E-26</td><td align="left" valign="top">110.83665</td><td align="left" valign="top">&#x02212;0.0202903</td><td align="left" valign="top">0.0346251</td><td align="left" valign="top">0.558</td></tr><tr><td align="left" valign="top">4</td><td align="left" valign="top">rs12054563</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.126677</td><td align="left" valign="top">0.0176431</td><td align="left" valign="top">6.97E-13</td><td align="left" valign="top">51.552027</td><td align="left" valign="top">&#x02212;0.0164525</td><td align="left" valign="top">0.0159578</td><td align="left" valign="top">0.3025</td></tr><tr><td align="left" valign="top">5</td><td align="left" valign="top">rs1560711</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.122379</td><td align="left" valign="top">0.0141465</td><td align="left" valign="top">5.11E-18</td><td align="left" valign="top">74.836901</td><td align="left" valign="top">&#x02212;0.0033405</td><td align="left" valign="top">0.0090041</td><td align="left" valign="top">0.7104</td></tr><tr><td align="left" valign="top">6</td><td align="left" valign="top">rs174529</td><td align="left" valign="top">C</td><td align="left" valign="top">T</td><td align="left" valign="top">&#x02212;0.0686342</td><td align="left" valign="top">0.0107211</td><td align="left" valign="top">1.54E-10</td><td align="left" valign="top">40.982878</td><td align="left" valign="top">&#x02212;0.0016235</td><td align="left" valign="top">0.0068503</td><td align="left" valign="top">0.8124</td></tr><tr><td align="left" valign="top">7</td><td align="left" valign="top">rs2066865</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.186112</td><td align="left" valign="top">0.0112369</td><td align="left" valign="top">1.30E-61</td><td align="left" valign="top">274.31889</td><td align="left" valign="top">&#x02212;0.0033999</td><td align="left" valign="top">0.0077623</td><td align="left" valign="top">0.6612</td></tr><tr><td align="left" valign="top">8</td><td align="left" valign="top">rs3756011</td><td align="left" valign="top">A</td><td align="left" valign="top">C</td><td align="left" valign="top">0.192712</td><td align="left" valign="top">0.0105525</td><td align="left" valign="top">1.65E-74</td><td align="left" valign="top">333.50841</td><td align="left" valign="top">0.000575</td><td align="left" valign="top">0.0067645</td><td align="left" valign="top">0.9326</td></tr><tr><td align="left" valign="top">9</td><td align="left" valign="top">rs57328376</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">0.0697584</td><td align="left" valign="top">0.0109198</td><td align="left" valign="top">1.68E-10</td><td align="left" valign="top">40.809724</td><td align="left" valign="top">&#x02212;0.0010062</td><td align="left" valign="top">0.0071873</td><td align="left" valign="top">0.8885</td></tr><tr><td align="left" valign="top">10</td><td align="left" valign="top">rs576123</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.237396</td><td align="left" valign="top">0.0104973</td><td align="left" valign="top">3.09E-113</td><td align="left" valign="top">511.43633</td><td align="left" valign="top">0.0183551</td><td align="left" valign="top">0.0086786</td><td align="left" valign="top">0.03441</td></tr><tr><td align="left" valign="top">11</td><td align="left" valign="top">rs5896</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.109291</td><td align="left" valign="top">0.0125852</td><td align="left" valign="top">3.82E-18</td><td align="left" valign="top">75.413406</td><td align="left" valign="top">0.020985</td><td align="left" valign="top">0.0096527</td><td align="left" valign="top">0.02974</td></tr><tr><td align="left" valign="top">12</td><td align="left" valign="top">rs6025</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.873415</td><td align="left" valign="top">0.0298388</td><td align="left" valign="top">2.42E-188</td><td align="left" valign="top">856.79828</td><td align="left" valign="top">0.0380118</td><td align="left" valign="top">0.0218836</td><td align="left" valign="top">0.08241</td></tr><tr><td align="left" valign="top">13</td><td align="left" valign="top">rs6060308</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.101587</td><td align="left" valign="top">0.0112359</td><td align="left" valign="top">1.55E-19</td><td align="left" valign="top">81.744876</td><td align="left" valign="top">&#x02212;0.0009288</td><td align="left" valign="top">0.0074901</td><td align="left" valign="top">0.9013</td></tr><tr><td align="left" valign="top">14</td><td align="left" valign="top">rs60681578</td><td align="left" valign="top">C</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.118392</td><td align="left" valign="top">0.0150029</td><td align="left" valign="top">2.99E-15</td><td align="left" valign="top">62.272211</td><td align="left" valign="top">0.0085067</td><td align="left" valign="top">0.0117172</td><td align="left" valign="top">0.4678</td></tr><tr><td align="left" valign="top">15</td><td align="left" valign="top">rs62350309</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.173509</td><td align="left" valign="top">0.0181448</td><td align="left" valign="top">1.15E-21</td><td align="left" valign="top">91.440721</td><td align="left" valign="top">0.0075114</td><td align="left" valign="top">0.0152982</td><td align="left" valign="top">0.6233</td></tr><tr><td align="left" valign="top">16</td><td align="left" valign="top">rs628094</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.0818781</td><td align="left" valign="top">0.0114389</td><td align="left" valign="top">8.19E-13</td><td align="left" valign="top">51.235029</td><td align="left" valign="top">&#x02212;0.0022354</td><td align="left" valign="top">0.0074021</td><td align="left" valign="top">0.7627</td></tr><tr><td align="left" valign="top">17</td><td align="left" valign="top">rs72708961</td><td align="left" valign="top">C</td><td align="left" valign="top">T</td><td align="left" valign="top">0.0891913</td><td align="left" valign="top">0.0159445</td><td align="left" valign="top">2.22E-08</td><td align="left" valign="top">31.291269</td><td align="left" valign="top">&#x02212;0.0170636</td><td align="left" valign="top">0.0090957</td><td align="left" valign="top">0.06059</td></tr><tr><td align="left" valign="top">18</td><td align="left" valign="top">rs7772305</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.0726964</td><td align="left" valign="top">0.0111586</td><td align="left" valign="top">7.28E-11</td><td align="left" valign="top">42.443031</td><td align="left" valign="top">0.016709</td><td align="left" valign="top">0.0086396</td><td align="left" valign="top">0.05311</td></tr><tr><td align="left" valign="top">19</td><td align="left" valign="top">rs80137017</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.208902</td><td align="left" valign="top">0.0177996</td><td align="left" valign="top">8.30E-32</td><td align="left" valign="top">137.74147</td><td align="left" valign="top">0.0152022</td><td align="left" valign="top">0.0099426</td><td align="left" valign="top">0.1262</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" colspan="4" valign="top">
<bold>Exposure: PE</bold>
</td><td align="left" colspan="3" valign="top">
<bold>Outcome: OSA (Campos et al)</bold>
</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">
<bold>SNP</bold>
</td><td align="left" valign="top">
<bold>EA</bold>
</td><td align="left" valign="top">
<bold>OA</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td><td align="left" valign="top">
<bold>F-statistic</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td></tr><tr><td align="left" valign="top">1</td><td align="left" valign="top">rs117210485</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.150787</td><td align="left" valign="top">0.0228699</td><td align="left" valign="top">4.30E-11</td><td align="left" valign="top">43.470964</td><td align="left" valign="top">&#x02212;0.0346523</td><td align="left" valign="top">0.0239146</td><td align="left" valign="top">0.1473</td></tr><tr><td align="left" valign="top">2</td><td align="left" valign="top">rs143620474</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.281243</td><td align="left" valign="top">0.0512263</td><td align="left" valign="top">4.01E-08</td><td align="left" valign="top">30.142375</td><td align="left" valign="top">0.0124988</td><td align="left" valign="top">0.0892769</td><td align="left" valign="top">0.8889</td></tr><tr><td align="left" valign="top">3</td><td align="left" valign="top">rs1481808</td><td align="left" valign="top">C</td><td align="left" valign="top">T</td><td align="left" valign="top">&#x02212;0.480929</td><td align="left" valign="top">0.0875759</td><td align="left" valign="top">3.98E-08</td><td align="left" valign="top">30.157318</td><td align="left" valign="top">&#x02212;0.0281243</td><td align="left" valign="top">0.0269648</td><td align="left" valign="top">0.297</td></tr><tr><td align="left" valign="top">4</td><td align="left" valign="top">rs1560711</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.144704</td><td align="left" valign="top">0.0202073</td><td align="left" valign="top">8.01E-13</td><td align="left" valign="top">51.279584</td><td align="left" valign="top">&#x02212;0.0033405</td><td align="left" valign="top">0.0090041</td><td align="left" valign="top">0.7104</td></tr><tr><td align="left" valign="top">5</td><td align="left" valign="top">rs2066865</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.227484</td><td align="left" valign="top">0.0158067</td><td align="left" valign="top">5.85E-47</td><td align="left" valign="top">207.11869</td><td align="left" valign="top">&#x02212;0.0033999</td><td align="left" valign="top">0.0077623</td><td align="left" valign="top">0.6612</td></tr><tr><td align="left" valign="top">6</td><td align="left" valign="top">rs28584824</td><td align="left" valign="top">A</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.155264</td><td align="left" valign="top">0.0279234</td><td align="left" valign="top">2.69E-08</td><td align="left" valign="top">30.917541</td><td align="left" valign="top">0.0324135</td><td align="left" valign="top">0.0191569</td><td align="left" valign="top">0.09056</td></tr><tr><td align="left" valign="top">7</td><td align="left" valign="top">rs3756011</td><td align="left" valign="top">A</td><td align="left" valign="top">C</td><td align="left" valign="top">0.234784</td><td align="left" valign="top">0.0149143</td><td align="left" valign="top">7.77E-56</td><td align="left" valign="top">247.81709</td><td align="left" valign="top">0.000575</td><td align="left" valign="top">0.0067645</td><td align="left" valign="top">0.9326</td></tr><tr><td align="left" valign="top">8</td><td align="left" valign="top">rs62350309</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.202534</td><td align="left" valign="top">0.0260372</td><td align="left" valign="top">7.33E-15</td><td align="left" valign="top">60.507237</td><td align="left" valign="top">0.0075114</td><td align="left" valign="top">0.0152982</td><td align="left" valign="top">0.6233</td></tr><tr><td align="left" valign="top">9</td><td align="left" valign="top">rs635634</td><td align="left" valign="top">C</td><td align="left" valign="top">T</td><td align="left" valign="top">&#x02212;0.239636</td><td align="left" valign="top">0.0177935</td><td align="left" valign="top">2.43E-41</td><td align="left" valign="top">181.37664</td><td align="left" valign="top">0.0139975</td><td align="left" valign="top">0.0096935</td><td align="left" valign="top">0.1488</td></tr><tr><td align="left" valign="top">10</td><td align="left" valign="top">rs77165492</td><td align="left" valign="top">C</td><td align="left" valign="top">T</td><td align="left" valign="top">0.209269</td><td align="left" valign="top">0.0275462</td><td align="left" valign="top">3.03E-14</td><td align="left" valign="top">57.714695</td><td align="left" valign="top">0.0013946</td><td align="left" valign="top">0.0114311</td><td align="left" valign="top">0.9026</td></tr><tr><td align="left" valign="top">11</td><td align="left" valign="top">rs80137017</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.230014</td><td align="left" valign="top">0.02543</td><td align="left" valign="top">1.50E-19</td><td align="left" valign="top">81.811776</td><td align="left" valign="top">0.0152022</td><td align="left" valign="top">0.0099426</td><td align="left" valign="top">0.1262</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" colspan="4" valign="top">
<bold>Exposure: DVT</bold>
</td><td align="left" colspan="3" valign="top">
<bold>Outcome: OSA (Campos et al)</bold>
</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">
<bold>SNP</bold>
</td><td align="left" valign="top">
<bold>EA</bold>
</td><td align="left" valign="top">
<bold>OA</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td><td align="left" valign="top">
<bold>F-statistic</bold>
</td><td align="left" valign="top">
<bold>Beta</bold>
</td><td align="left" valign="top">
<bold>SE</bold>
</td><td align="left" valign="top">
<bold><italic>p</italic></bold>
<bold>-Value</bold>
</td></tr><tr><td align="left" valign="top">1</td><td align="left" valign="top">rs116997538</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.466245</td><td align="left" valign="top">0.0534583</td><td align="left" valign="top">2.74E-18</td><td align="left" valign="top">76.067315</td><td align="left" valign="top">&#x02212;0.0202903</td><td align="left" valign="top">0.0346251</td><td align="left" valign="top">0.558</td></tr><tr><td align="left" valign="top">2</td><td align="left" valign="top">rs13377102</td><td align="left" valign="top">A</td><td align="left" valign="top">T</td><td align="left" valign="top">&#x02212;0.233255</td><td align="left" valign="top">0.0255094</td><td align="left" valign="top">6.02E-20</td><td align="left" valign="top">83.610619</td><td align="left" valign="top">0.0085579</td><td align="left" valign="top">0.0096591</td><td align="left" valign="top">0.3759</td></tr><tr><td align="left" valign="top">3</td><td align="left" valign="top">rs2066865</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.184507</td><td align="left" valign="top">0.0161145</td><td align="left" valign="top">2.36E-30</td><td align="left" valign="top">131.09678</td><td align="left" valign="top">&#x02212;0.0033999</td><td align="left" valign="top">0.0077623</td><td align="left" valign="top">0.6612</td></tr><tr><td align="left" valign="top">4</td><td align="left" valign="top">rs576123</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">&#x02212;0.297682</td><td align="left" valign="top">0.014983</td><td align="left" valign="top">7.70E-88</td><td align="left" valign="top">394.73678</td><td align="left" valign="top">0.0183551</td><td align="left" valign="top">0.0086786</td><td align="left" valign="top">0.03441</td></tr><tr><td align="left" valign="top">5</td><td align="left" valign="top">rs5896</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.141024</td><td align="left" valign="top">0.017945</td><td align="left" valign="top">3.88E-15</td><td align="left" valign="top">61.75884</td><td align="left" valign="top">0.020985</td><td align="left" valign="top">0.0096527</td><td align="left" valign="top">0.02974</td></tr><tr><td align="left" valign="top">6</td><td align="left" valign="top">rs6025</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">1.10439</td><td align="left" valign="top">0.0393903</td><td align="left" valign="top">5.71E-173</td><td align="left" valign="top">786.07929</td><td align="left" valign="top">0.0380118</td><td align="left" valign="top">0.0218836</td><td align="left" valign="top">0.08241</td></tr><tr><td align="left" valign="top">7</td><td align="left" valign="top">rs6060237</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">0.168453</td><td align="left" valign="top">0.0198214</td><td align="left" valign="top">1.92E-17</td><td align="left" valign="top">72.225216</td><td align="left" valign="top">0.0060526</td><td align="left" valign="top">0.0101724</td><td align="left" valign="top">0.5518</td></tr><tr><td align="left" valign="top">8</td><td align="left" valign="top">rs60681578</td><td align="left" valign="top">C</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.137615</td><td align="left" valign="top">0.021627</td><td align="left" valign="top">1.98E-10</td><td align="left" valign="top">40.489181</td><td align="left" valign="top">0.0085067</td><td align="left" valign="top">0.0117172</td><td align="left" valign="top">0.4678</td></tr><tr><td align="left" valign="top">9</td><td align="left" valign="top">rs62350309</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.162704</td><td align="left" valign="top">0.0259998</td><td align="left" valign="top">3.90E-10</td><td align="left" valign="top">39.161241</td><td align="left" valign="top">0.0075114</td><td align="left" valign="top">0.0152982</td><td align="left" valign="top">0.6233</td></tr><tr><td align="left" valign="top">10</td><td align="left" valign="top">rs666870</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.0924832</td><td align="left" valign="top">0.0159069</td><td align="left" valign="top">6.10E-09</td><td align="left" valign="top">33.802949</td><td align="left" valign="top">0.0074616</td><td align="left" valign="top">0.0067221</td><td align="left" valign="top">0.2669</td></tr><tr><td align="left" valign="top">11</td><td align="left" valign="top">rs7308002</td><td align="left" valign="top">A</td><td align="left" valign="top">G</td><td align="left" valign="top">0.0978174</td><td align="left" valign="top">0.01576</td><td align="left" valign="top">5.41E-10</td><td align="left" valign="top">38.522974</td><td align="left" valign="top">&#x02212;0.0023644</td><td align="left" valign="top">0.0068533</td><td align="left" valign="top">0.7298</td></tr><tr><td align="left" valign="top">12</td><td align="left" valign="top">rs7772305</td><td align="left" valign="top">G</td><td align="left" valign="top">A</td><td align="left" valign="top">&#x02212;0.100251</td><td align="left" valign="top">0.016057</td><td align="left" valign="top">4.28E-10</td><td align="left" valign="top">38.980608</td><td align="left" valign="top">0.016709</td><td align="left" valign="top">0.0086396</td><td align="left" valign="top">0.05311</td></tr><tr><td align="left" valign="top">13</td><td align="left" valign="top">rs9865118</td><td align="left" valign="top">T</td><td align="left" valign="top">C</td><td align="left" valign="top">0.0863804</td><td align="left" valign="top">0.0151814</td><td align="left" valign="top">1.27E-08</td><td align="left" valign="top">32.374776</td><td align="left" valign="top">&#x02212;0.0005648</td><td align="left" valign="top">0.0066442</td><td align="left" valign="top">0.9323</td></tr></tbody></table><table-wrap-foot><fn id="FN23110519-5"><p>Abbreviations: DVT, deep vein thrombosis; EA, effect allele; MR, Mendelian randomization; OA, other allele; OSA, obstructive sleep apnea; PE, pulmonary embolism; SE, standard error; SNP, single-nucleotide polymorphism; VTE, venous thromboembolism.</p></fn><fn id="FN23110519-6"><p>
Note: F-statistic&#x02009;=&#x02009;(Beta/SE)
<sup>2</sup>
, represents the strength of each instrumental variable.
</p></fn></table-wrap-foot></table-wrap></sec><sec><title>Effects of OSA on VTE</title><p><xref rid="FI23110519-2" ref-type="fig">Fig. 2</xref>
shows the estimates of the effects for OSA on VTE, PE, and DVT. In the initial MR analysis using the OSA (Jiang et al) dataset, the random-effects IVW method revealed no significant association between OSA and the risk of VTE (odds ratio [OR]: 0.964, 95% confidence interval [CI]: 0.914-1.016,
<italic>p</italic>
&#x02009;=&#x02009;0.172), PE (OR: 0.929, 95% CI: 0.857&#x02013;1.006,
<italic>p</italic>
&#x02009;=&#x02009;0.069), PE (OR: 0.929, 95% CI: 0.857&#x02013;1.006,
<italic>p</italic>
&#x02009;=&#x02009;0.069), and DVT (OR: 1.001, 95% CI: 0.936&#x02013;1.071,
<italic>p</italic>
&#x02009;=&#x02009;0.973). No heterogeneity was observed using the Cochran Q test (all
<italic>p</italic>
*&#x02009;&#x0003e;&#x02009;0.05). The MR&#x02013;Egger intercept test (all
<italic>p</italic>
**&#x02009;&#x0003e;&#x02009;0.05) and the MR-PRESSO global test (all
<italic>p</italic>
***&#x02009;&#x0003e;&#x02009;0.05) failed to detect any evidence of pleiotropy.
</p><fig id="FI23110519-2"><label>Fig. 2</label><caption><p>
The genetic association of OSA with VTE/PE/DVT. OSA, obstructive sleep apnea; VTE, venous thromboembolism; PE, pulmonary embolism; DVT, deep vein thrombosis; MR, mendelian randomization; IVW, inverse variance weighted; PRESSO, pleiotropy residual sum and outlier; P*, represents P for heterogeneity test; P**, represents P for MR-Egger intercept; P***, represents P for MR-PRESSO global test.
</p></caption><graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="10-1055-a-2308-2290-i23110519-2"/></fig><p>
The validation analysis using genetic variants of OSA (Campos et al) yielded similar results. Notably, heterogeneity was observed in the sensitivity analysis for OSA (Campos et al) and VTE (
<italic>p</italic>
*&#x02009;=&#x02009;0.018). However, considering the random-effects IVW model employed, the level of heterogeneity was deemed acceptable.
<xref rid="JR23110519-28" ref-type="bibr">28</xref>
Despite the presence of outliers suggested by the MR-PRESSO global test (
<italic>p</italic>
&#x02009;=&#x02009;0.015), no significant association between OSA and VTE (OR: 1.071, 95% CI: 0.917&#x02013;1.251,
<italic>p</italic>
&#x02009;=&#x02009;0.396) was found after excluding an outlier (rs7106583). In addition, none of the three complementary MR methods supported a genetic association between OSA and VTE.
</p></sec><sec><title>Effects of VTE on OSA</title><p>
We conducted reverse MR analysis to further evaluate the effects of VTE (including PE and DVT) on OSA. Both MR analyses yielded consistent results, indicating no significant effects of VTE, PE, and DVT on OSA (see
<xref rid="FI23110519-3" ref-type="fig">Fig. 3</xref>
). Moreover, the Cochran Q test revealed no heterogeneity (all
<italic>p</italic>
*&#x02009;&#x0003e;&#x02009;0.05), and both the MR&#x02013;Egger intercept test and the MR-PRESSO global test found no evidence of pleiotropy (all
<italic>p</italic>
**&#x02009;&#x0003e;&#x02009;0.05 and
<italic>p</italic>
***&#x02009;&#x0003e;&#x02009;0.05, respectively) (see
<xref rid="FI23110519-3" ref-type="fig">Fig. 3</xref>
). In summary, a range of sensitivities confirmed the reliability of the MR results.
</p><fig id="FI23110519-3"><label>Fig. 3</label><caption><p>
The genetic association of VTE/PE/DVT with OSA. OSA, obstructive sleep apnea; VTE, venous thromboembolism; PE, pulmonary embolism; DVT, deep vein thrombosis; MR, mendelian randomization; IVW, inverse variance weighted; PRESSO, pleiotropy residual sum and outlier; P*, represents P for heterogeneity test; P**, represents P for MR-Egger intercept; P***, represents P for MR-PRESSO global test.
</p></caption><graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="10-1055-a-2308-2290-i23110519-3"/></fig></sec></sec><sec><title>Discussion</title><p>In this study, we conducted a comprehensive two-sample MR analysis to explore the genetic association between OSA and VTE. Our MR findings did not yield evidence of a significant association between OSA and VTE from a genetic standpoint.</p><p>
Our findings contradict some previous observational studies suggesting a link between susceptibility to OSA and an increased risk of VTE.
<xref rid="JR23110519-29" ref-type="bibr">29</xref>
<xref rid="JR23110519-30" ref-type="bibr">30</xref>
<xref rid="JR23110519-31" ref-type="bibr">31</xref>
<xref rid="JR23110519-32" ref-type="bibr">32</xref>
</p><p>
However, these studies were hindered by inadequate consideration of confounding factors, particularly obesity, along with methodological flaws and small sample sizes. Obesity is widely recognized as a significant risk factor for both OSA
<xref rid="JR23110519-33" ref-type="bibr">33</xref>
and VTE.
<xref rid="JR23110519-34" ref-type="bibr">34</xref>
Therefore, it is crucial not to overlook the impact of obesity in striving for a deeper understanding of the potential association between OSA and VTE. Notably, a cohort study involving 31,309 subjects indicated a higher likelihood of VTE development among patients with more severe OSA. Yet, this association disappeared upon adjusting for confounders, notably obesity levels.
<xref rid="JR23110519-35" ref-type="bibr">35</xref>
Thus, it is plausible that the observed association between OSA and VTE could be attributed to obesity confounding. Additionally, Aman and his colleagues' report yielded consistent results, suggesting that OSA does not elevate the risk of VTE after adjusting for obesity confounding.
<xref rid="JR23110519-36" ref-type="bibr">36</xref>
</p><p>MR is a robust analytical method that employs genetic variation as IVs to deduce the genetic association between exposure and outcome. Consequently, it effectively controls for confounders induced by environmental factors and mitigates reverse causality bias. In this study, we meticulously screened genetic variants and thoroughly accounted for the effects of obesity levels to procure reliable IVs for inferring the genetic association between OSA and VTE. To mitigate bias and enhance the reliability of our MR findings, we devised initial and validation MR analyses supplemented by a series of sensitivity analyses, drawing upon datasets sourced from various origins. Notably, neither MR analysis provided evidence supporting a genetic association between OSA and VTE. Moreover, a succession of sensitivity analyses served to bolster the robustness of our MR results. These findings indicate that, although diverging from some previous observational studies, our results are reliable and corroborate the conclusions drawn from the MR study.</p><p>
While our MR study did not find evidence supporting a genetic association between OSA and VTE, it remains possible that OSA could influence the onset or progression of VTE. Virchow's triad depicts three major factors inducing VTE: endothelial injury, venous stasis, and hypercoagulability.
<xref rid="JR23110519-37" ref-type="bibr">37</xref>
The pathophysiologic mechanism linking OSA and VTE remains unknown but may be associated with OSA's capacity to affect the three classical mechanistic pathways of Virchow's triad.
<xref rid="JR23110519-38" ref-type="bibr">38</xref>
Intermittent hypoxia, a signature feature of OSA, can induce oxidative stress and activate inflammatory markers, further damaging the vascular endothelium.
<xref rid="JR23110519-39" ref-type="bibr">39</xref>
<xref rid="JR23110519-40" ref-type="bibr">40</xref>
OSA-associated hemodynamic alterations and reduced physical activities may result in venous stasis.
<xref rid="JR23110519-41" ref-type="bibr">41</xref>
A growing number of studies have demonstrated a strong correlation between OSA and hypercoagulability. A retrospective cohort study aimed at assessing coagulation in patients with OSA suggested that patients with moderate to severe OSA experienced elevated markers of blood coagulability, primarily evidenced by shortened prothrombin time, compared to healthy individuals.
<xref rid="JR23110519-42" ref-type="bibr">42</xref>
Two additional studies of thrombotic parameters found that patients with OSA possessed higher levels of the thrombin&#x02013;antithrombin complex.
<xref rid="JR23110519-43" ref-type="bibr">43</xref>
<xref rid="JR23110519-44" ref-type="bibr">44</xref>
Furthermore, several coagulation factors, such as fibrinogen, coagulation factor VII, coagulation factor XII, and vascular hemophilic factor, which play a crucial role in the coagulation process, are elevated in patients with OSA.
<xref rid="JR23110519-45" ref-type="bibr">45</xref>
Collectively, this evidence supports that patients with OSA are in a state of hypercoagulability, facilitating our understanding of the underlying pathophysiologic mechanisms between OSA and VTE. Considering these potential mechanisms, future large-scale studies are necessary to thoroughly explore the potential association between OSA and VTE, delving into greater depth.
</p><p>The greatest strength of this study is that the bidirectional two-sample MR analysis designed based on summary data from large-scale GWAS was used for the first time to investigate the genetic association between OSA and VTE. Furthermore, to bolster the robustness of the findings and mitigate bias, we conducted initial and validated MR analyses using two independent OSA GWAS datasets. Subsequently, a series of sensitivity analyses provided further validation and affirmed the robustness of the results. However, our study also has several limitations. First, it was exclusively centered on European individuals, thereby constraining the generalizability of our findings to other ethnicities or ancestries. Second, the lack of individual-level data in the summary-level statistics prevented us from stratifying the study population by important factors such as age or sex. Lastly, there is a possibility of sample overlap between the exposure and outcome datasets, but the F-statistics of the IVs selected in the MR analysis were sufficiently strong to mitigate the potential effects of weak instrumental bias.</p></sec><sec><title>Conclusion</title><p>In conclusion, our MR study did not uncover genetic evidence supporting an association between OSA and VTE, including DVT and PE. This implies that the association between OSA and VTE reported in some previous observational studies may rely on alternative pathways to function, rather than being directly linked to the diseases themselves.</p></sec></body><back><sec><boxed-text content-type="backinfo"><p>
<bold>What is known about this topic?</bold>
</p><list list-type="bullet"><list-item><p>Previous studies have linked obstructive sleep apnea (OSA) and venous thromboembolism (VTE).</p></list-item><list-item><p>Existing studies regarding the association between OSA and VTE are somewhat controversial.</p></list-item><list-item><p>The various aspects of the association between OSA and VTE remain to be evaluated.</p></list-item></list><p>
<bold>What does this paper add?</bold>
</p><list list-type="bullet"><list-item><p>There were no significant effects of OSA on VTE.</p></list-item><list-item><p>Similarly, VTE also had no significant effects on OSA.</p></list-item><list-item><p>The association between OSA and VTE may arise through pathways other than the diseases themselves.</p></list-item></list></boxed-text></sec><ack><title>Acknowledgment</title><p>We would also like to thank Yao Xiaoxia from Lianjiang No.3 Middle School for correcting the grammar in this article.</p></ack><fn-group><fn fn-type="COI-statement" id="d35e168"><p><bold>Conflict of Interest</bold> None declared.</p></fn></fn-group><fn-group><title>Data Availability Statement</title><fn id="FN23110519-7"><p>The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.</p></fn></fn-group><fn-group><title>Authors' Contribution</title><fn id="FN23110519-8"><p>All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.</p></fn></fn-group><fn-group><fn id="FN23110519-1"><label>*</label><p>
<italic>These authors contributed equally to this study.</italic>
</p></fn></fn-group><ref-list><title>References</title><ref id="JR23110519-1"><label>1</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>S H</given-names></name><name><surname>Chen</surname><given-names>W S</given-names></name><name><surname>Tang</surname><given-names>S E</given-names></name></person-group><etal/><article-title>Benzodiazepines associated with acute respiratory failure in patients with obstructive sleep apnea</article-title><source>Front Pharmacol</source><year>2019</year><volume>9</volume><fpage>1513</fpage><pub-id pub-id-type="pmid">30666205</pub-id>
</mixed-citation></ref><ref id="JR23110519-2"><label>2</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Innes</surname><given-names>C R</given-names></name><name><surname>Kelly</surname><given-names>P T</given-names></name><name><surname>Hlavac</surname><given-names>M</given-names></name><name><surname>Melzer</surname><given-names>T R</given-names></name><name><surname>Jones</surname><given-names>R D</given-names></name></person-group><article-title>Decreased regional cerebral perfusion in moderate-severe obstructive sleep apnoea during wakefulness</article-title><source>Sleep</source><year>2015</year><volume>38</volume><issue>05</issue><fpage>699</fpage><lpage>706</lpage><pub-id pub-id-type="pmid">25669185</pub-id>
</mixed-citation></ref><ref id="JR23110519-3"><label>3</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Senaratna</surname><given-names>C V</given-names></name><name><surname>Perret</surname><given-names>J L</given-names></name><name><surname>Lodge</surname><given-names>C J</given-names></name></person-group><etal/><article-title>Prevalence of obstructive sleep apnea in the general population: a systematic review</article-title><source>Sleep Med Rev</source><year>2017</year><volume>34</volume><fpage>70</fpage><lpage>81</lpage><pub-id pub-id-type="pmid">27568340</pub-id>
</mixed-citation></ref><ref id="JR23110519-4"><label>4</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bai</surname><given-names>J</given-names></name><name><surname>Wen</surname><given-names>H</given-names></name><name><surname>Tai</surname><given-names>J</given-names></name></person-group><etal/><article-title>Altered spontaneous brain activity related to neurologic and sleep dysfunction in children with obstructive sleep apnea syndrome</article-title><source>Front Neurosci</source><year>2021</year><volume>15</volume><fpage>595412</fpage><pub-id pub-id-type="pmid">34867137</pub-id>
</mixed-citation></ref><ref id="JR23110519-5"><label>5</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marin</surname><given-names>J M</given-names></name><name><surname>Agusti</surname><given-names>A</given-names></name><name><surname>Villar</surname><given-names>I</given-names></name></person-group><etal/><article-title>Association between treated and untreated obstructive sleep apnea and risk of hypertension</article-title><source>JAMA</source><year>2012</year><volume>307</volume><issue>20</issue><fpage>2169</fpage><lpage>2176</lpage><pub-id pub-id-type="pmid">22618924</pub-id>
</mixed-citation></ref><ref id="JR23110519-6"><label>6</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Redline</surname><given-names>S</given-names></name><name><surname>Yenokyan</surname><given-names>G</given-names></name><name><surname>Gottlieb</surname><given-names>D J</given-names></name></person-group><etal/><article-title>Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study</article-title><source>Am J Respir Crit Care Med</source><year>2010</year><volume>182</volume><issue>02</issue><fpage>269</fpage><lpage>277</lpage><pub-id pub-id-type="pmid">20339144</pub-id>
</mixed-citation></ref><ref id="JR23110519-7"><label>7</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mesarwi</surname><given-names>O</given-names></name><name><surname>Malhotra</surname><given-names>A</given-names></name></person-group><article-title>Obstructive sleep apnea and pulmonary hypertension: a bidirectional relationship</article-title><source>J Clin Sleep Med</source><year>2020</year><volume>16</volume><fpage>1223</fpage><lpage>1224</lpage><pub-id pub-id-type="pmid">32807290</pub-id>
</mixed-citation></ref><ref id="JR23110519-8"><label>8</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Piccirillo</surname><given-names>F</given-names></name><name><surname>Crispino</surname><given-names>S P</given-names></name><name><surname>Buzzelli</surname><given-names>L</given-names></name><name><surname>Segreti</surname><given-names>A</given-names></name><name><surname>Incalzi</surname><given-names>R A</given-names></name><name><surname>Grigioni</surname><given-names>F</given-names></name></person-group><article-title>A state-of-the-art review on sleep apnea syndrome and heart failure</article-title><source>Am J Cardiol</source><year>2023</year><volume>195</volume><fpage>57</fpage><lpage>69</lpage><pub-id pub-id-type="pmid">37011555</pub-id>
</mixed-citation></ref><ref id="JR23110519-9"><label>9</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Glise Sandblad</surname><given-names>K</given-names></name><name><surname>Rosengren</surname><given-names>A</given-names></name><name><surname>S&#x000f6;rbo</surname><given-names>J</given-names></name><name><surname>Jern</surname><given-names>S</given-names></name><name><surname>Hansson</surname><given-names>P O</given-names></name></person-group><article-title>Pulmonary embolism and deep vein thrombosis-comorbidities and temporary provoking factors in a register-based study of 1.48 million people</article-title><source>Res Pract Thromb Haemost</source><year>2022</year><volume>6</volume><issue>04</issue><fpage>e12714</fpage><pub-id pub-id-type="pmid">35677029</pub-id>
</mixed-citation></ref><ref id="JR23110519-10"><label>10</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Raj</surname><given-names>R</given-names></name><name><surname>Paturi</surname><given-names>A</given-names></name><name><surname>Ahmed</surname><given-names>M A</given-names></name><name><surname>Thomas</surname><given-names>S E</given-names></name><name><surname>Gorantla</surname><given-names>V R</given-names></name></person-group><article-title>Obstructive sleep apnea as a risk factor for venous thromboembolism: a systematic review</article-title><source>Cureus</source><year>2022</year><volume>14</volume><issue>02</issue><fpage>e22729</fpage><pub-id pub-id-type="pmid">35371730</pub-id>
</mixed-citation></ref><ref id="JR23110519-11"><label>11</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lin</surname><given-names>C C</given-names></name><name><surname>Keller</surname><given-names>J J</given-names></name><name><surname>Kang</surname><given-names>J H</given-names></name><name><surname>Hsu</surname><given-names>T C</given-names></name><name><surname>Lin</surname><given-names>H C</given-names></name></person-group><article-title>Obstructive sleep apnea is associated with an increased risk of venous thromboembolism</article-title><source>J Vasc Surg Venous Lymphat Disord</source><year>2013</year><volume>1</volume><issue>02</issue><fpage>139</fpage><lpage>145</lpage><pub-id pub-id-type="pmid">26992334</pub-id>
</mixed-citation></ref><ref id="JR23110519-12"><label>12</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Peng</surname><given-names>Y H</given-names></name><name><surname>Liao</surname><given-names>W C</given-names></name><name><surname>Chung</surname><given-names>W S</given-names></name></person-group><etal/><article-title>Association between obstructive sleep apnea and deep vein thrombosis / pulmonary embolism: a population-based retrospective cohort study</article-title><source>Thromb Res</source><year>2014</year><volume>134</volume><issue>02</issue><fpage>340</fpage><lpage>345</lpage><pub-id pub-id-type="pmid">24972845</pub-id>
</mixed-citation></ref><ref id="JR23110519-13"><label>13</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nepveu</surname><given-names>O</given-names></name><name><surname>Orione</surname><given-names>C</given-names></name><name><surname>Tromeur</surname><given-names>C</given-names></name></person-group><etal/><article-title>Association between obstructive sleep apnea and venous thromboembolism recurrence: results from a French cohort</article-title><source>Thromb J</source><year>2022</year><volume>20</volume><issue>01</issue><fpage>1</fpage><pub-id pub-id-type="pmid">34983561</pub-id>
</mixed-citation></ref><ref id="JR23110519-14"><label>14</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dabbagh</surname><given-names>O</given-names></name><name><surname>Sabharwal</surname><given-names>M</given-names></name><name><surname>Hassan</surname><given-names>O</given-names></name></person-group><etal/><article-title>Obstructive sleep apnea is an independent risk factor for venous thromboembolism among females not males</article-title><source>Chest</source><year>2010</year><volume>138</volume><fpage>937A</fpage><lpage>937A</lpage><pub-id pub-id-type="pmid">20522573</pub-id>
</mixed-citation></ref><ref id="JR23110519-15"><label>15</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bosanquet</surname><given-names>J P</given-names></name><name><surname>Bade</surname><given-names>B C</given-names></name><name><surname>Zia</surname><given-names>M F</given-names></name></person-group><etal/><article-title>Patients with venous thromboembolism appear to have higher prevalence of obstructive sleep apnea than the general population</article-title><source>Clin Appl Thromb Hemost</source><year>2011</year><volume>17</volume><issue>06</issue><fpage>E119</fpage><lpage>E124</lpage><pub-id pub-id-type="pmid">21159707</pub-id>
</mixed-citation></ref><ref id="JR23110519-16"><label>16</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xue</surname><given-names>A</given-names></name><name><surname>Jiang</surname><given-names>L</given-names></name><name><surname>Zhu</surname><given-names>Z</given-names></name></person-group><etal/><article-title>Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes</article-title><source>Nat Commun</source><year>2021</year><volume>12</volume><issue>01</issue><fpage>20211</fpage><pub-id pub-id-type="pmid">33436567</pub-id>
</mixed-citation></ref><ref id="JR23110519-17"><label>17</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pu</surname><given-names>B</given-names></name><name><surname>Gu</surname><given-names>P</given-names></name><name><surname>Zheng</surname><given-names>C</given-names></name><name><surname>Ma</surname><given-names>L</given-names></name><name><surname>Zheng</surname><given-names>X</given-names></name><name><surname>Zeng</surname><given-names>Z</given-names></name></person-group><article-title>Self-reported and genetically predicted effects of coffee intake on rheumatoid arthritis: epidemiological studies and Mendelian randomization analysis</article-title><source>Front Nutr</source><year>2022</year><volume>9</volume><fpage>926190</fpage><pub-id pub-id-type="pmid">36172525</pub-id>
</mixed-citation></ref><ref id="JR23110519-18"><label>18</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jiang</surname><given-names>L</given-names></name><name><surname>Zheng</surname><given-names>Z</given-names></name><name><surname>Fang</surname><given-names>H</given-names></name><name><surname>Yang</surname><given-names>J</given-names></name></person-group><article-title>A generalized linear mixed model association tool for biobank-scale data</article-title><source>Nat Genet</source><year>2021</year><volume>53</volume><issue>11</issue><fpage>1616</fpage><lpage>1621</lpage><pub-id pub-id-type="pmid">34737426</pub-id>
</mixed-citation></ref><ref id="JR23110519-19"><label>19</label><mixed-citation publication-type="journal"><collab>23andMe Research Team </collab><person-group person-group-type="author"><name><surname>Campos</surname><given-names>A I</given-names></name><name><surname>Ingold</surname><given-names>N</given-names></name><name><surname>Huang</surname><given-names>Y</given-names></name></person-group><etal/><article-title>Discovery of genomic loci associated with sleep apnea risk through multi-trait GWAS analysis with snoring</article-title><source>Sleep</source><year>2023</year><volume>46</volume><issue>03</issue><fpage>46</fpage></mixed-citation></ref><ref id="JR23110519-20"><label>20</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Feng</surname><given-names>R</given-names></name><name><surname>Lu</surname><given-names>M</given-names></name><name><surname>Xu</surname><given-names>J</given-names></name></person-group><etal/><article-title>Pulmonary embolism and 529 human blood metabolites: genetic correlation and two-sample Mendelian randomization study</article-title><source>BMC Genom Data</source><year>2022</year><volume>23</volume><issue>01</issue><fpage>69</fpage><pub-id pub-id-type="pmid">36038828</pub-id>
</mixed-citation></ref><ref id="JR23110519-21"><label>21</label><mixed-citation publication-type="journal"><collab>ISGC Intracranial Aneurysm Working Group* </collab><person-group person-group-type="author"><name><surname>Molenberg</surname><given-names>R</given-names></name><name><surname>Thio</surname><given-names>C HL</given-names></name><name><surname>Aalbers</surname><given-names>M W</given-names></name></person-group><etal/><article-title>Sex hormones and risk of aneurysmal subarachnoid hemorrhage: a Mendelian randomization study</article-title><source>Stroke</source><year>2022</year><volume>53</volume><issue>09</issue><fpage>2870</fpage><lpage>2875</lpage><pub-id pub-id-type="pmid">35652345</pub-id>
</mixed-citation></ref><ref id="JR23110519-22"><label>22</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>S H</given-names></name><name><surname>Keenan</surname><given-names>B T</given-names></name><name><surname>Wiemken</surname><given-names>A</given-names></name></person-group><etal/><article-title>Effect of weight loss on upper airway anatomy and the apnea-hypopnea index. the importance of tongue fat</article-title><source>Am J Respir Crit Care Med</source><year>2020</year><volume>201</volume><issue>06</issue><fpage>718</fpage><lpage>727</lpage><pub-id pub-id-type="pmid">31918559</pub-id>
</mixed-citation></ref><ref id="JR23110519-23"><label>23</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hotoleanu</surname><given-names>C</given-names></name></person-group><article-title>Association between obesity and venous thromboembolism</article-title><source>Med Pharm Rep</source><year>2020</year><volume>93</volume><issue>02</issue><fpage>162</fpage><lpage>168</lpage><pub-id pub-id-type="pmid">32478322</pub-id>
</mixed-citation></ref><ref id="JR23110519-24"><label>24</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhao</surname><given-names>H</given-names></name><name><surname>Jin</surname><given-names>X</given-names></name></person-group><article-title>Causal associations between dietary antioxidant vitamin intake and lung cancer: a Mendelian randomization study</article-title><source>Front Nutr</source><year>2022</year><volume>9</volume><fpage>965911</fpage><pub-id pub-id-type="pmid">36118777</pub-id>
</mixed-citation></ref><ref id="JR23110519-25"><label>25</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tang</surname><given-names>B</given-names></name><name><surname>Wang</surname><given-names>Y</given-names></name><name><surname>Jiang</surname><given-names>X</given-names></name></person-group><etal/><article-title>Genetic variation in targets of antidiabetic drugs and Alzheimer disease risk: a Mendelian randomization study</article-title><source>Neurology</source><year>2022</year><volume>99</volume><issue>07</issue><fpage>e650</fpage><lpage>e659</lpage><pub-id pub-id-type="pmid">35654594</pub-id>
</mixed-citation></ref><ref id="JR23110519-26"><label>26</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dong</surname><given-names>S S</given-names></name><name><surname>Zhang</surname><given-names>K</given-names></name><name><surname>Guo</surname><given-names>Y</given-names></name></person-group><etal/><article-title>Phenome-wide investigation of the causal associations between childhood BMI and adult trait outcomes: a two-sample Mendelian randomization study</article-title><source>Genome Med</source><year>2021</year><volume>13</volume><issue>01</issue><fpage>48</fpage><pub-id pub-id-type="pmid">33771188</pub-id>
</mixed-citation></ref><ref id="JR23110519-27"><label>27</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>W</given-names></name><name><surname>Xiao</surname><given-names>J</given-names></name><name><surname>Ji</surname><given-names>J</given-names></name><name><surname>Chen</surname><given-names>L</given-names></name></person-group><article-title>Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study</article-title><source>eLife</source><year>2021</year><volume>10</volume><fpage>10</fpage></mixed-citation></ref><ref id="JR23110519-28"><label>28</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>X</given-names></name><name><surname>Kong</surname><given-names>J</given-names></name><name><surname>Pan</surname><given-names>J</given-names></name></person-group><etal/><article-title>Kidney damage causally affects the brain cortical structure: a Mendelian randomization study</article-title><source>EBioMedicine</source><year>2021</year><volume>72</volume><fpage>103592</fpage><pub-id pub-id-type="pmid">34619639</pub-id>
</mixed-citation></ref><ref id="JR23110519-29"><label>29</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arnulf</surname><given-names>I</given-names></name><name><surname>Merino-Andreu</surname><given-names>M</given-names></name><name><surname>Perrier</surname><given-names>A</given-names></name><name><surname>Birolleau</surname><given-names>S</given-names></name><name><surname>Similowski</surname><given-names>T</given-names></name><name><surname>Derenne</surname><given-names>J P</given-names></name></person-group><article-title>Obstructive sleep apnea and venous thromboembolism</article-title><source>JAMA</source><year>2002</year><volume>287</volume><issue>20</issue><fpage>2655</fpage><lpage>2656</lpage></mixed-citation></ref><ref id="JR23110519-30"><label>30</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chou</surname><given-names>K T</given-names></name><name><surname>Huang</surname><given-names>C C</given-names></name><name><surname>Chen</surname><given-names>Y M</given-names></name></person-group><etal/><article-title>Sleep apnea and risk of deep vein thrombosis: a non-randomized, pair-matched cohort study</article-title><source>Am J Med</source><year>2012</year><volume>125</volume><issue>04</issue><fpage>374</fpage><lpage>380</lpage><pub-id pub-id-type="pmid">22444103</pub-id>
</mixed-citation></ref><ref id="JR23110519-31"><label>31</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alonso-Fern&#x000e1;ndez</surname><given-names>A</given-names></name><name><surname>de la Pe&#x000f1;a</surname><given-names>M</given-names></name><name><surname>Romero</surname><given-names>D</given-names></name></person-group><etal/><article-title>Association between obstructive sleep apnea and pulmonary embolism</article-title><source>Mayo Clin Proc</source><year>2013</year><volume>88</volume><issue>06</issue><fpage>579</fpage><lpage>587</lpage><pub-id pub-id-type="pmid">23578813</pub-id>
</mixed-citation></ref><ref id="JR23110519-32"><label>32</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ambrosetti</surname><given-names>M</given-names></name><name><surname>Lucioni</surname><given-names>A</given-names></name><name><surname>Ageno</surname><given-names>W</given-names></name><name><surname>Conti</surname><given-names>S</given-names></name><name><surname>Neri</surname><given-names>M</given-names></name></person-group><article-title>Is venous thromboembolism more frequent in patients with obstructive sleep apnea syndrome?</article-title><source>J Thromb Haemost</source><year>2004</year><volume>2</volume><issue>10</issue><fpage>1858</fpage><lpage>1860</lpage><pub-id pub-id-type="pmid">15456508</pub-id>
</mixed-citation></ref><ref id="JR23110519-33"><label>33</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reutrakul</surname><given-names>S</given-names></name><name><surname>Mokhlesi</surname><given-names>B</given-names></name></person-group><article-title>Obstructive sleep apnea and diabetes: a state of the art review</article-title><source>Chest</source><year>2017</year><volume>152</volume><issue>05</issue><fpage>1070</fpage><lpage>1086</lpage><pub-id pub-id-type="pmid">28527878</pub-id>
</mixed-citation></ref><ref id="JR23110519-34"><label>34</label><mixed-citation publication-type="journal"><collab>INVENT Consortium </collab><person-group person-group-type="author"><name><surname>Lindstr&#x000f6;m</surname><given-names>S</given-names></name><name><surname>Germain</surname><given-names>M</given-names></name><name><surname>Crous-Bou</surname><given-names>M</given-names></name></person-group><etal/><article-title>Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study</article-title><source>Hum Genet</source><year>2017</year><volume>136</volume><issue>07</issue><fpage>897</fpage><lpage>902</lpage><pub-id pub-id-type="pmid">28528403</pub-id>
</mixed-citation></ref><ref id="JR23110519-35"><label>35</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Genuardi</surname><given-names>M V</given-names></name><name><surname>Rathore</surname><given-names>A</given-names></name><name><surname>Ogilvie</surname><given-names>R P</given-names></name></person-group><etal/><article-title>Incidence of VTE in patients with OSA: a cohort study</article-title><source>Chest</source><year>2022</year><volume>161</volume><issue>04</issue><fpage>1073</fpage><lpage>1082</lpage><pub-id pub-id-type="pmid">34914977</pub-id>
</mixed-citation></ref><ref id="JR23110519-36"><label>36</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aman</surname><given-names>R</given-names></name><name><surname>Michael</surname><given-names>V G</given-names></name><name><surname>Rachel</surname><given-names>P O</given-names></name></person-group><etal/><article-title>Obstructive sleep apnea does not increase risk of venous thromboembolism</article-title><source>American Thoracic Society</source><year>2019</year><fpage>A4459</fpage><lpage>A4459</lpage></mixed-citation></ref><ref id="JR23110519-37"><label>37</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Esmon</surname><given-names>C T</given-names></name></person-group><article-title>Basic mechanisms and pathogenesis of venous thrombosis</article-title><source>Blood Rev</source><year>2009</year><volume>23</volume><issue>05</issue><fpage>225</fpage><lpage>229</lpage><pub-id pub-id-type="pmid">19683659</pub-id>
</mixed-citation></ref><ref id="JR23110519-38"><label>38</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Garc&#x000ed;a-Ortega</surname><given-names>A</given-names></name><name><surname>Ma&#x000f1;as</surname><given-names>E</given-names></name><name><surname>L&#x000f3;pez-Reyes</surname><given-names>R</given-names></name></person-group><etal/><article-title>Obstructive sleep apnoea and venous thromboembolism: pathophysiological links and clinical implications</article-title><source>Eur Respir J</source><year>2019</year><volume>53</volume><issue>02</issue><fpage>53</fpage></mixed-citation></ref><ref id="JR23110519-39"><label>39</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xiong</surname><given-names>H</given-names></name><name><surname>Lao</surname><given-names>M</given-names></name><name><surname>Wang</surname><given-names>L</given-names></name></person-group><etal/><article-title>The incidence of cancer is increased in hospitalized adult patients with obstructive sleep apnea in China: a retrospective cohort study</article-title><source>Front Oncol</source><year>2022</year><volume>12</volume><fpage>856121</fpage><pub-id pub-id-type="pmid">35433429</pub-id>
</mixed-citation></ref><ref id="JR23110519-40"><label>40</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Holt</surname><given-names>A</given-names></name><name><surname>Bjerre</surname><given-names>J</given-names></name><name><surname>Zareini</surname><given-names>B</given-names></name></person-group><etal/><article-title>Sleep apnea, the risk of developing heart failure, and potential benefits of continuous positive airway pressure (CPAP) therapy</article-title><source>J Am Heart Assoc</source><year>2018</year><volume>7</volume><issue>13</issue><fpage>e008684</fpage><pub-id pub-id-type="pmid">29934418</pub-id>
</mixed-citation></ref><ref id="JR23110519-41"><label>41</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alonso-Fern&#x000e1;ndez</surname><given-names>A</given-names></name><name><surname>Toledo-Pons</surname><given-names>N</given-names></name><name><surname>Garc&#x000ed;a-R&#x000ed;o</surname><given-names>F</given-names></name></person-group><article-title>Obstructive sleep apnea and venous thromboembolism: overview of an emerging relationship</article-title><source>Sleep Med Rev</source><year>2020</year><volume>50</volume><fpage>101233</fpage><pub-id pub-id-type="pmid">31838272</pub-id>
</mixed-citation></ref><ref id="JR23110519-42"><label>42</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hong</surname><given-names>S N</given-names></name><name><surname>Yun</surname><given-names>H C</given-names></name><name><surname>Yoo</surname><given-names>J H</given-names></name><name><surname>Lee</surname><given-names>S H</given-names></name></person-group><article-title>Association between hypercoagulability and severe obstructive sleep apnea</article-title><source>JAMA Otolaryngol Head Neck Surg</source><year>2017</year><volume>143</volume><issue>10</issue><fpage>996</fpage><lpage>1002</lpage><pub-id pub-id-type="pmid">28817760</pub-id>
</mixed-citation></ref><ref id="JR23110519-43"><label>43</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Robinson</surname><given-names>G V</given-names></name><name><surname>Pepperell</surname><given-names>J C</given-names></name><name><surname>Segal</surname><given-names>H C</given-names></name><name><surname>Davies</surname><given-names>R J</given-names></name><name><surname>Stradling</surname><given-names>J R</given-names></name></person-group><article-title>Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials</article-title><source>Thorax</source><year>2004</year><volume>59</volume><issue>09</issue><fpage>777</fpage><lpage>782</lpage><pub-id pub-id-type="pmid">15333855</pub-id>
</mixed-citation></ref><ref id="JR23110519-44"><label>44</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>von K&#x000e4;nel</surname><given-names>R</given-names></name><name><surname>Loredo</surname><given-names>J S</given-names></name><name><surname>Powell</surname><given-names>F L</given-names></name><name><surname>Adler</surname><given-names>K A</given-names></name><name><surname>Dimsdale</surname><given-names>J E</given-names></name></person-group><article-title>Short-term isocapnic hypoxia and coagulation activation in patients with sleep apnea</article-title><source>Clin Hemorheol Microcirc</source><year>2005</year><volume>33</volume><issue>04</issue><fpage>369</fpage><lpage>377</lpage><pub-id pub-id-type="pmid">16317246</pub-id>
</mixed-citation></ref><ref id="JR23110519-45"><label>45</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zolotoff</surname><given-names>C</given-names></name><name><surname>Bertoletti</surname><given-names>L</given-names></name><name><surname>Gozal</surname><given-names>D</given-names></name></person-group><etal/><article-title>Obstructive sleep apnea, hypercoagulability, and the blood-brain barrier</article-title><source>J Clin Med</source><year>2021</year><volume>10</volume><issue>14</issue><fpage>3099</fpage><pub-id pub-id-type="pmid">34300265</pub-id>
</mixed-citation></ref></ref-list></back></article>