{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T17:56:12Z","timestamp":1794333372321,"version":"4.9.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T00:00:00Z","timestamp":1560384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006636","name":"Swedish Research Council for Health, Working Life and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006636","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["204623\/Z\/16\/Z"],"award-info":[{"award-number":["204623\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>The causal role of adiposity for several cardiovascular diseases (CVDs) is unclear. Our primary aim was to apply the Mendelian randomization design to investigate the associations of body mass index (BMI) with 13 CVDs and arterial hypertension. We also assessed the roles of fat mass and fat-free mass on the same outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Single-nucleotide polymorphisms associated with BMI and fat mass and fat-free mass indices were used as instrumental variables to estimate the associations with the cardiovascular conditions among 367 703 UK Biobank participants. After correcting for multiple testing, genetically predicted BMI was significantly positively associated with eight outcomes, including and with decreasing magnitude of association: aortic valve stenosis, heart failure, deep vein thrombosis, arterial hypertension, peripheral artery disease, coronary artery disease, atrial fibrillation, and pulmonary embolism. The odds ratio (OR) per 1\u2009kg\/m2 increase in BMI ranged from 1.06 [95% confidence interval (CI) 1.02\u20131.11; P\u2009=\u20092.6\u2009\u00d7\u200910\u22123] for pulmonary embolism to 1.13 (95% CI 1.05\u20131.21; P\u2009=\u20091.2\u2009\u00d7\u200910\u22123) for aortic valve stenosis. There was suggestive evidence of positive associations of genetically predicted fat mass index with nine outcomes (P\u2009&amp;lt;\u20090.05). The strongest magnitude of association was with aortic valve stenosis (OR per 1\u2009kg\/m2 increase in fat mass index 1.46, 95% CI 1.13\u20131.88; P\u2009=\u20093.9\u2009\u00d7\u200910\u22123). There was suggestive evidence of inverse associations of fat-free mass index with atrial fibrillation, ischaemic stroke, and abdominal aortic aneurysm.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study provides evidence that higher BMI and particularly fat mass index are associated with increased risk of aortic valve stenosis and most other cardiovascular conditions.<\/jats:p>\n                  <jats:p\/>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehz388","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T19:16:33Z","timestamp":1558379793000},"page":"221-226","source":"Crossref","is-referenced-by-count":419,"title":["Body mass index and body composition in relation to 14 cardiovascular conditions in UK Biobank: a Mendelian randomization study"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-0341","authenticated-orcid":false,"given":"Susanna C","family":"Larsson","sequence":"first","affiliation":[{"name":"Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet , Nobels v\u00e4g 13, SE-17177 Stockholm, Sweden"},{"name":"Department of Surgical Sciences, Uppsala University , Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"B\u00e4ck","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Molecular Medicine, Karolinska Institutet , Stockholm, Sweden"},{"name":"Heart and Vascular Theme \u2013 Division of Valvular and Coronary Disease, Karolinska University Hospital , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1495-2470","authenticated-orcid":false,"given":"Jessica M B","family":"Rees","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge , Cambridge, UK"},{"name":"Edinburgh Clinical Trials Unit, Usher, Institute of Population Health Sciences and Informatics, University of Edinburgh , Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy M","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge , Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-8760","authenticated-orcid":false,"given":"Stephen","family":"Burgess","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge , Cambridge, UK"},{"name":"MRC Biostatistics Unit, University of Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,13]]},"reference":[{"key":"2022102608524559800_ehz388-B1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1614362","article-title":"Health effects of overweight and obesity in 195 countries over 25 years","volume":"377","author":"Afshin","year":"2017","journal-title":"N Engl J Med"},{"key":"2022102608524559800_ehz388-B2","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1016\/S0140-6736(18)32207-4","article-title":"Changes in health in the countries of the UK and 150 English Local Authority areas 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"392","author":"Steel","year":"2018","journal-title":"Lancet"},{"key":"2022102608524559800_ehz388-B3","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1093\/ije\/dyv094","article-title":"Adiposity as a cause of cardiovascular disease: a Mendelian randomization study","volume":"44","author":"Hagg","year":"2015","journal-title":"Int J Epidemiol"},{"key":"2022102608524559800_ehz388-B4","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1161\/CIRCULATIONAHA.116.026560","article-title":"Causal associations of adiposity and body fat distribution with coronary heart disease, stroke subtypes, and type 2 diabetes mellitus: a Mendelian randomization analysis","volume":"135","author":"Dale","year":"2017","journal-title":"Circulation"},{"key":"2022102608524559800_ehz388-B5","doi-asserted-by":"crossref","first-page":"e1001212","DOI":"10.1371\/journal.pmed.1001212","article-title":"The effect of elevated body mass index on ischemic heart disease risk: causal estimates from a Mendelian randomisation approach","volume":"9","author":"Nordestgaard","year":"2012","journal-title":"PLoS Med"},{"key":"2022102608524559800_ehz388-B6","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1001\/jamacardio.2016.5804","article-title":"Association of body mass index with cardiometabolic disease in the UK BIOBANK: a Mendelian randomization study","volume":"2","author":"Lyall","year":"2017","journal-title":"JAMA Cardiol"},{"key":"2022102608524559800_ehz388-B7","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1161\/ATVBAHA.114.304015","article-title":"Carotid plaque, intima-media thickness, and incident aortic stenosis: a prospective cohort study","volume":"34","author":"Martinsson","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2022102608524559800_ehz388-B8","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s10654-014-9936-x","article-title":"Assessment of risk factors for developing incident aortic stenosis: the Tromso Study","volume":"29","author":"Eveborn","year":"2014","journal-title":"Eur J Epidemiol"},{"key":"2022102608524559800_ehz388-B9","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1093\/eurheartj\/ehx140","article-title":"Overall and abdominal obesity and incident aortic valve stenosis: two prospective cohort studies","volume":"38","author":"Larsson","year":"2017","journal-title":"Eur Heart J"},{"key":"2022102608524559800_ehz388-B10","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1212\/WNL.0000000000003171","article-title":"Adiposity and ischemic and hemorrhagic stroke: prospective study in women and meta-analysis","volume":"87","author":"Kroll","year":"2016","journal-title":"Neurology"},{"key":"2022102608524559800_ehz388-B11","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/bjs.8983","article-title":"Obesity and abdominal aortic aneurysm","volume":"100","author":"Stackelberg","year":"2013","journal-title":"Br J Surg"},{"key":"2022102608524559800_ehz388-B12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ije\/dyg070","article-title":"\u2018Mendelian randomization\u2019: can genetic epidemiology contribute to understanding environmental determinants of disease?","volume":"32","author":"Davey Smith","year":"2003","journal-title":"Int J Epidemiol"},{"key":"2022102608524559800_ehz388-B13","doi-asserted-by":"crossref","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age","volume":"12","author":"Sudlow","year":"2015","journal-title":"PLoS Med"},{"key":"2022102608524559800_ehz388-B14","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature14177","article-title":"Genetic studies of body mass index yield new insights for obesity biology","volume":"518","author":"Locke","year":"2015","journal-title":"Nature"},{"key":"2022102608524559800_ehz388-B15","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/s41467-018-08000-4","article-title":"Genome-wide association study of body fat distribution identifies adiposity loci and sex-specific genetic effects","volume":"10","author":"Rask-Andersen","year":"2019","journal-title":"Nat Commun"},{"key":"2022102608524559800_ehz388-B16","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":"2022102608524559800_ehz388-B17","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/EDE.0000000000000559","article-title":"Sensitivity analyses for robust causal inference from Mendelian randomization analyses with multiple genetic variants","volume":"28","author":"Burgess","year":"2017","journal-title":"Epidemiology"},{"key":"2022102608524559800_ehz388-B18","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":"2022102608524559800_ehz388-B19","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":"2022102608524559800_ehz388-B20","article-title":"An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings","author":"Sanderson","year":"2018","journal-title":"Int J Epidemiol"},{"key":"2022102608524559800_ehz388-B21","first-page":"383","article-title":"A meta-analysis of the association of obesity with abdominal aortic aneurysm presence","volume":"34","author":"Takagi","year":"2015","journal-title":"Int Angiol"},{"key":"2022102608524559800_ehz388-B22","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s00439-017-1811-x","article-title":"Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study","volume":"136","author":"Lindstrom","year":"2017","journal-title":"Hum Genet"},{"key":"2022102608524559800_ehz388-B23","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.atherosclerosis.2015.12.034","article-title":"Obesity and peripheral arterial disease: a Mendelian randomization analysis","volume":"247","author":"Huang","year":"2016","journal-title":"Atherosclerosis"},{"key":"2022102608524559800_ehz388-B24","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":"2022102608524559800_ehz388-B25","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1212\/WNL.0000000000004173","article-title":"Type 2 diabetes, glucose, insulin, BMI, and ischemic stroke subtypes: Mendelian randomization study","volume":"89","author":"Larsson","year":"2017","journal-title":"Neurology"},{"key":"2022102608524559800_ehz388-B26","doi-asserted-by":"crossref","DOI":"10.1093\/eurheartj\/ehz003","article-title":"Body composition and atrial fibrillation: a Mendelian randomization study","author":"Tikkanen","year":"2019","journal-title":"Eur Heart J"},{"key":"2022102608524559800_ehz388-B27","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/ng.3390","article-title":"Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index","volume":"47","author":"Yang","year":"2015","journal-title":"Nat Genet"},{"key":"2022102608524559800_ehz388-B28","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1093\/eurheartj\/ehw106","article-title":"2016 European Guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR)","volume":"37","author":"Piepoli","year":"2016","journal-title":"Eur Heart J"}],"container-title":["European Heart Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurheartj\/article-pdf\/41\/2\/221\/46639450\/eurheartj_41_2_221.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurheartj\/article-pdf\/41\/2\/221\/46639450\/eurheartj_41_2_221.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T08:55:20Z","timestamp":1666774520000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurheartj\/article\/41\/2\/221\/5514076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,13]]},"references-count":28,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,6,13]]},"published-print":{"date-parts":[[2020,1,7]]}},"URL":"https:\/\/doi.org\/10.1093\/eurheartj\/ehz388","relation":{},"ISSN":["0195-668X","1522-9645"],"issn-type":[{"value":"0195-668X","type":"print"},{"value":"1522-9645","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,1,7]]},"published":{"date-parts":[[2019,6,13]]}}}