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Genetics of Height and Risk of Atrial Fibrillation: A Mendelian Randomization Study

By Michael G Levin, Renae Judy, Dipender Gill, Marijana Vujkovic, Regeneron Genetics Center, Matthew C. Hyman, Saman Nazarian, Daniel J. Rader, Benjamin F. Voight, Scott M Damrauer

Posted 30 Dec 2019
medRxiv DOI: 10.1101/2019.12.23.19015743

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 = 5x10-42). 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.

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