Genetics of Height and Risk of Atrial Fibrillation: A Mendelian Randomization Study
Genetics of Height and Risk of Atrial Fibrillation: A Mendelian Randomization Study
ABSTRACT ObjectiveTo determine whether height has a causal effect on risk of atrial fibrillation DesignMendelian randomization study SettingGenome-wide association studies of height and atrial fibrillation; Penn Medicine Biobank ParticipantsMultiethnic (predominantly European ancestry) participants in genome-wide association studies of height (693,529 individuals) and atrial fibrillation (65,446 cases and 522,744 controls); 7,023 Penn Medicine Biobank participants of European ancestry ExposuresHeight, cardiometabolic risk factors for atrial fibrillation, and randomly allocated genetic variants strongly associated with these traits Main outcome measureRisk of atrial fibrillation (measured in odds ratio) ResultsAt the population level, a 1 standard deviation increase in genetically-predicted height was associated with increased odds of AF (Odds ratio [OR] 1.34; 95% Confidence Interval [CI] 1.29 to 1.40; p = 5×10?42). These findings remained consistent in sensitivity analyses that were robust to the presence of pleiotropic variants. Results from analyses considering individual-participant data were similar, even after adjustment for clinical covariates, including left atrial size. ConclusionGenetically predicted height is a positive causal risk factor for AF. This finding raises the possibility of investigating height/growth-related pathways as a means for gaining novel mechanistic insights to atrial fibrillation, as well as incorporating height into population screening strategies for atrial fibrillation.
Nazarian Saman、Rader Daniel J.、Gill Dipender、Judy Renae、Voight Benjamin F.、Vujkovic Marijana、Hyman Matthew C.、Regeneron Genetics Center、Damrauer Scott M.、Levin Michael G.
Division of Cardiovascular Medicine, University of Pennsylvania Perelman School of Medicine||Department of Medicine, University of Pennsylvania Perelman School of MedicineDepartment of Medicine, University of Pennsylvania Perelman School of Medicine||Department of Genetics, University of Pennsylvania Perelman School of Medicine||Institute for Translational Medicine and Therapeutics, University of Pennsylvania Perelman School of MedicineDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDepartment of Surgery, University of Pennsylvania Perelman School of MedicineDepartment of Genetics, University of Pennsylvania Perelman School of Medicine||Institute for Translational Medicine and Therapeutics, University of Pennsylvania Perelman School of Medicine||Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of MedicineDepartment of Medicine, University of Pennsylvania Perelman School of Medicine||Corporal Michael J. Crescenz VA Medical CenterDivision of Cardiovascular Medicine, University of Pennsylvania Perelman School of Medicine||Department of Medicine, University of Pennsylvania Perelman School of MedicineRegeneron Genetics CenterCorporal Michael J. Crescenz VA Medical Center||Department of Surgery, University of Pennsylvania Perelman School of MedicineDivision of Cardiovascular Medicine, University of Pennsylvania Perelman School of Medicine||Department of Medicine, University of Pennsylvania Perelman School of Medicine||Corporal Michael J. Crescenz VA Medical Center
医学研究方法基础医学遗传学
Nazarian Saman,Rader Daniel J.,Gill Dipender,Judy Renae,Voight Benjamin F.,Vujkovic Marijana,Hyman Matthew C.,Regeneron Genetics Center,Damrauer Scott M.,Levin Michael G..Genetics of Height and Risk of Atrial Fibrillation: A Mendelian Randomization Study[EB/OL].(2025-03-28)[2025-05-11].https://www.medrxiv.org/content/10.1101/2019.12.23.19015743.点此复制
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