Rachel L Kember1,2, Michael G Levin3,2, Diana L Cousminer1,4,5, Noah Tsao6, Renae Judy6, Gayatri M Schur7, Steven A Lubitz8,9, Patrick T Ellinor8,9, Shana E McCormack7,10, Struan F A Grant1,7,4,5, Daniel J Rader1,3, Benjamin F Voight1,11,12, Scott M Damrauer6,2. 1. From the Departments of Genetics (R.L.K., D.L.C., S.F.A.G., D.J.R., B.F.V.), University of Pennsylvania. 2. Corporal Michael J. Crescenz VA Medical Center (R.L.K., M.G.L., S.M.D.). 3. Medicine (M.G.L., D.J.R.), University of Pennsylvania. 4. Division of Human Genetics (D.L.C., S.F.A.G.), Children's Hospital of Philadelphia, PA. 5. Center for Spatial and Functional Genomics (D.L.C., S.F.A.G.), Children's Hospital of Philadelphia, PA. 6. Surgery (N.T., R.J., S.M.D.), University of Pennsylvania. 7. Pediatrics (G.M.S., S.E.M., S.F.A.G.), University of Pennsylvania. 8. Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston (S.A.L., P.T.E.). 9. Program in Medical and Population Genetics, The Broad Institute of MIT & Harvard, Cambridge, MA (S.A.L., P.T.E.). 10. Division of Endocrinology and Diabetes (S.E.M.), Children's Hospital of Philadelphia, PA. 11. Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine (B.F.V.), University of Pennsylvania. 12. Institute for Translational Medicine and Therapeutics (B.F.V.), University of Pennsylvania.
Abstract
BACKGROUND: Atrial fibrillation is a common cardiovascular disorder, characterized by irregular electrical activity in the upper chambers of the heart. Both chronic cardiometabolic risk factors and genetics have been shown to contribute to the development of atrial fibrillation. Birthweight has also been associated with risk of atrial fibrillation. METHODS: In the current study, we utilized a genetic approach to study the effect of birthweight on atrial fibrillation. We used 2-sample Mendelian randomization to consider the impact of birthweight on incident atrial fibrillation using summary data from the Early Growth Genetics Consortium GWAS of birthweight and a large biobank-based GWAS of atrial fibrillation. RESULTS: Using the framework of 2-sample Mendelian randomization, we found that a 1-SD genetic elevation of birthweight was associated with increased risk of atrial fibrillation (odds ratio, 1.27 [95% CI, 1.14-1.41]; P=1×10-5) with sensitivity analyses demonstrating robustness of this result. CONCLUSIONS: Our findings clarify the directionality of the relationship between birthweight and atrial fibrillation, supporting the growing body of evidence that intrauterine growth has a lifelong impact on cardiovascular health.
BACKGROUND:Atrial fibrillation is a common cardiovascular disorder, characterized by irregular electrical activity in the upper chambers of the heart. Both chronic cardiometabolic risk factors and genetics have been shown to contribute to the development of atrial fibrillation. Birthweight has also been associated with risk of atrial fibrillation. METHODS: In the current study, we utilized a genetic approach to study the effect of birthweight on atrial fibrillation. We used 2-sample Mendelian randomization to consider the impact of birthweight on incident atrial fibrillation using summary data from the Early Growth Genetics Consortium GWAS of birthweight and a large biobank-based GWAS of atrial fibrillation. RESULTS: Using the framework of 2-sample Mendelian randomization, we found that a 1-SD genetic elevation of birthweight was associated with increased risk of atrial fibrillation (odds ratio, 1.27 [95% CI, 1.14-1.41]; P=1×10-5) with sensitivity analyses demonstrating robustness of this result. CONCLUSIONS: Our findings clarify the directionality of the relationship between birthweight and atrial fibrillation, supporting the growing body of evidence that intrauterine growth has a lifelong impact on cardiovascular health.
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