{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T13:21:30Z","timestamp":1788009690323,"version":"build-2784847793"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,2]],"date-time":"2022-01-02T00:00:00Z","timestamp":1641081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>It remains unclear whether the association between obstructive sleep apnoea (OSA), a form of sleep-disordered breathing (SDB), and atrial fibrillation (AF) is causal or mediated by shared co-morbidities such as obesity. Existing observational studies are conflicting and limited by confounding and reverse causality. We performed Mendelian randomisation (MR) to investigate the causal relationships between SDB, body mass index (BMI) and AF. Single-nucleotide polymorphisms associated with SDB (n = 29) and BMI (n = 453) were selected as instrumental variables to investigate the effects of SDB and BMI on AF, using genetic association data on 55,114 AF cases and 482,295 controls. Primary analysis was conducted using inverse-variance weighted MR. Higher genetically predicted SDB and BMI were associated with increased risk of AF (OR per log OR increase in snoring liability 2.09 (95% CI 1.10\u20133.98), p = 0.03; OR per 1-SD increase in BMI 1.33 (95% CI 1.24\u20131.42), p &lt; 0.001). The association between SDB and AF was not observed in sensitivity analyses, whilst associations between BMI and AF remained consistent. Similarly, in multivariable MR, SDB was not associated with AF after adjusting for BMI (OR 0.68 (95% CI 0.42\u20131.10), p = 0.12). Higher BMI remained associated with increased risk of AF after adjusting for OSA (OR 1.40 (95% CI 1.30\u20131.51), p &lt; 0.001). Elevated BMI appears causal for AF, independent of SDB. Our data suggest that the association between SDB, in general, and AF is attributable to mediation or confounding from obesity, though we cannot exclude that more severe SDB phenotypes (i.e., OSA) are causal for AF.<\/jats:p>","DOI":"10.3390\/genes13010104","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T22:51:50Z","timestamp":1641250310000},"page":"104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Sleep Disordered Breathing, Obesity and Atrial Fibrillation: A Mendelian Randomisation Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Maddalena","family":"Ardissino","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London W12 0NN, UK"},{"name":"Nuffield Department of Population Health, Old Road Campus, University of Oxford, Oxford OX3 7LF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4726-157X","authenticated-orcid":false,"given":"Rohin K.","family":"Reddy","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A. W.","family":"Slob","sequence":"additional","affiliation":[{"name":"MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran H. K.","family":"Patel","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George\u2019s University Hospitals NHS Foundation Trust, London SW17 0QT, UK"},{"name":"Clinical Pharmacology and Therapeutics Section, Institute for Infection and Immunity, St George\u2019s, University of London, London SW17 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7312-7078","authenticated-orcid":false,"given":"Dipender","family":"Gill","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George\u2019s University Hospitals NHS Foundation Trust, London SW17 0QT, UK"},{"name":"Clinical Pharmacology and Therapeutics Section, Institute for Infection and Immunity, St George\u2019s, University of London, London SW17 0RE, UK"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, UK"},{"name":"Novo Nordisk Research Centre Oxford, Old Road Campus, Oxford OX3 7FZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8681-4368","authenticated-orcid":false,"given":"Fu Siong","family":"Ng","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/eurheartj\/ehaa612","article-title":"2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC","volume":"42","author":"Hindricks","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s00392-015-0859-7","article-title":"The importance of sleep-disordered breathing in cardiovascular disease","volume":"104","author":"Linz","year":"2015","journal-title":"Clin. Res. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1093\/aje\/kws342","article-title":"Increased prevalence of sleep-disordered breathing in adults","volume":"177","author":"Peppard","year":"2013","journal-title":"Am. J. Epidemiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1161\/01.CIR.0000136587.68725.8E","article-title":"Association of atrial fibrillation and obstructive sleep apnea","volume":"110","author":"Gami","year":"2004","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.ahj.2014.12.024","article-title":"Impact of obstructive sleep apnea and continuous positive airway pressure therapy on outcomes in patients with atrial fibrillation-Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF)","volume":"169","author":"Holmqvist","year":"2015","journal-title":"Am. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1378\/chest.15-0229","article-title":"Severity of OSA is an independent predictor of incident atrial fibrillation hospitalization in a large sleep-clinic cohort","volume":"148","author":"Cadby","year":"2015","journal-title":"Chest"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1093\/europace\/euu066","article-title":"Efficacy of catheter ablation of atrial fibrillation in patients with obstructive sleep apnoea with and without continuous positive airway pressure treatment: A meta-analysis of observational studies","volume":"16","author":"Li","year":"2014","journal-title":"Europace"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jacc.2006.08.060","article-title":"Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation","volume":"49","author":"Gami","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1001\/archinternmed.2009.138","article-title":"Nocturnal Arrhythmias across a spectrum of obstructive and central sleep-disordered breathing in older men: Outcomes of sleep disorders in older men (MrOS sleep) study","volume":"169","author":"Mehra","year":"2009","journal-title":"Arch. Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/jce.14336","article-title":"Impact of a nurse-led limited risk factor modification program on arrhythmia outcomes in patients with atrial fibrillation undergoing catheter ablation","volume":"31","author":"Yaeger","year":"2020","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.5664\/jcsm.7976","article-title":"The Effect of Positive Airway Pressure Treatment of Obstructive and Central Sleep Apnea on the Recurrence of Atrial Fibrillation\/Flutter Postintervention","volume":"15","author":"Srivali","year":"2019","journal-title":"J. Clin. Sleep Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ijcard.2018.11.100","article-title":"The impact of continuous positive airway pressure treatment on the recurrence of atrial fibrillation post cardioversion: A randomized controlled trial","volume":"278","author":"Caples","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1164\/rccm.202011-4133OC","article-title":"Effect of Continuous Positive Airway Pressure on Arrhythmia in Atrial Fibrillation and Sleep Apnea: A Randomized Controlled Trial","volume":"204","author":"Traaen","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jacep.2015.04.004","article-title":"Obesity and the Risk of Incident, Post-Operative, and Post-Ablation Atrial Fibrillation: A Meta-Analysis of 626,603 Individuals in 51 Studies","volume":"1","author":"Wong","year":"2015","journal-title":"JACC Clin. Electrophysiol."},{"key":"ref_15","first-page":"1294","article-title":"Epicardial fat and atrial fibrillation: Current evidence, potential mechanisms, clinical implications, and future directions","volume":"38","author":"Wong","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1378\/chest.09-0360","article-title":"Interactions between obesity and obstructive sleep apnea: Implications for treatment","volume":"137","author":"Caples","year":"2010","journal-title":"Chest"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1001\/archinte.165.20.2408","article-title":"Progression and regression of sleep-disordered breathing with changes in weight: The Sleep Heart Health Study","volume":"165","author":"Newman","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1097\/00004872-199917090-00009","article-title":"Recent weight gain in patients with newly diagnosed obstructive sleep apnea","volume":"17","author":"Phillips","year":"1999","journal-title":"J. Hypertens."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1002\/sim.3034","article-title":"Mendelian randomization: Using genes as instruments for making causal inferences in epidemiology","volume":"27","author":"Lawlor","year":"2008","journal-title":"Stat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chen, W., Cai, X., Yan, H., and Pan, Y. (2021). Causal Effect of Obstructive Sleep Apnea on Atrial Fibrillation: A Mendelian Randomization Study. J. Am. Heart Assoc., e022560. Epub ahead of print.","DOI":"10.1161\/JAHA.121.022560"},{"key":"ref_21","unstructured":"(2019). STROBE-MR Steering Group: STROBE-MR: Guidelines for strengthening the reporting of Mendelian randomization studies. PeerJ."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1093\/hmg\/ddy271","article-title":"Meta-analysis of genome-wide association studies for height and body mass index in \u223c700000 individuals of European ancestry","volume":"27","author":"Yengo","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/s41467-020-14625-1","article-title":"Insights into the aetiology of snoring from observational angd genetic investigations in the UK Biobank","volume":"11","author":"Campos","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/s41588-018-0133-9","article-title":"Multi-ethnic genome-wide association study for atrial fibrillation","volume":"50","author":"Roselli","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"Elife"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1093\/ije\/dyt179","article-title":"Calculating statistical power in Mendelian randomization studies","volume":"42","author":"Brion","year":"2013","journal-title":"Int. J. Epidemiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"186","DOI":"10.12688\/wellcomeopenres.15555.2","article-title":"Guidelines for performing Mendelian randomization investigations","volume":"4","author":"Burgess","year":"2020","journal-title":"Wellcome Open Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/gepi.22295","article-title":"A comparison of robust Mendelian randomization methods using summary data","volume":"44","author":"Slob","year":"2020","journal-title":"Genet. Epidemiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","article-title":"Interpreting findings from Mendelian randomization using the MR-Egger method","volume":"32","author":"Burgess","year":"2017","journal-title":"Eur. J. Epidemiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rees, J.M.B., Wood, A.M., Dudbridge, F., and Burgess, S. (2019). Robust methods in Mendelian randomization via penalization of heterogeneous causal estimates. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222362"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1093\/ije\/dyx034","article-title":"MendelianRandomization: An R package for performing Mendelian randomization analyses using summarized data","volume":"46","author":"Yavorska","year":"2017","journal-title":"Int. J. Epidemiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1161\/CIRCULATIONAHA.116.024921","article-title":"Genetic Obesity and the Risk of Atrial Fibrillation: Causal Estimates from Mendelian Randomization","volume":"135","author":"Chatterjee","year":"2017","journal-title":"Circulation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/eurheartj\/ehz388","article-title":"Body mass index and body composition in relation to 14 cardiovascular conditions in UK Biobank: A Mendelian randomization study","volume":"41","author":"Larsson","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.hrthm.2012.08.043","article-title":"Obesity results in progressive atrial structural and electrical remodeling: Implications for atrial fibrillation","volume":"10","author":"Abed","year":"2013","journal-title":"Heart Rhythm"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1001\/jama.2013.280521","article-title":"Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: A randomized clinical trial","volume":"310","author":"Abed","year":"2013","journal-title":"JAMA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1093\/eurheartj\/ehx739","article-title":"Targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent atrial fibrillation: Results of the RACE 3 trial","volume":"39","author":"Rienstra","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/j.hrthm.2012.03.024","article-title":"Determinants of atrial fibrillation in an animal model of obesity and acute obstructive sleep apnea","volume":"9","author":"Iwasaki","year":"2012","journal-title":"Heart Rhythm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1136\/jech.44.4.257","article-title":"Declaring independence: Why we should be cautious","volume":"44","author":"Smith","year":"1990","journal-title":"J. Epidemiol. Community Health"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1056\/NEJMc1409673","article-title":"Coronary Heart Disease and Genetic Variants with Low Phospholipase A2 Activity","volume":"372","author":"Polfus","year":"2015","journal-title":"N. Engl. J. Med."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/1\/104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:35:57Z","timestamp":1760362557000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/1\/104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,2]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["genes13010104"],"URL":"https:\/\/doi.org\/10.3390\/genes13010104","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,2]]}}}