Abstract
Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death1. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10−8). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.
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Study concept and design was determined by P.T.E., K.L.L., C.M.A., B.P.K., M.K.C., J.D., H.V., A.H., Y.N., D.M.R., A.G.U., A.B.N., Y.L., T. Tanaka, B.H.C.S., S.B.F., D.D., S.R.H., E.J.B., V.G. and S. Kääb. Acquisition of data was performed by P.T.E., C.M.A., N.L.G., J.C.B., M.K.C., M.D., J.D.R., A.P., M.F.S., J.D., N.L.S., J.D.S., R.W., J.I.R., L.J.L., T.B.H., U.V., A.H., E.Z.S., M.K., U.B.T., D.C., T.F., R.M., B.M.P., T.M., S.P., H.-E.W., J.C.M.W., A.G.U., F.R., M.S., A.B.N., Y.L., M.H.G., B.H.C.S., A.A., S.R.H., E.J.B., V.G., B.P., H.L., B.F.V., M.B., W.H.L.K. and S. Kääb. Analysis and interpretation of data were performed by P.T.E., K.L.L., N.L.G., M.D.R., A.V.S., D.E.A., M.M.-N., B.P.K., S.A.L., J.C.B., M.D., K.O., J.D.R., J.G.S., M.F.S., K.L., J.D., N.L.S., K.M.R., J.I.R., R.W.D., U.V., G.L., T. Tsunoda, N.S., N.K., B.M.P., S. Kathiresan, D.M.R., B.M., Y.L., M.H.G., D.D., S.R.H., H.L., S.X. and E.J.B. Drafting of the manuscript was carried out by P.T.E., K.L.L., B.P.K., S.A.L. and S. Kääb. Critical revision of the manuscript for important intellectual content was carried out by C.M.A., N.L.G., A.V.S., D.E.A., B.P.K., J.C.B., M.K.C., M.D., J.G.S., A.P., M.F.S., J.D., N.L.S., J.D.S., M.R., K.M.R., D.R.V.W., J.W.M., R.W., J.I.R., L.J.L., T.B.H., U.V., H.V., D.J.M., A.H., L.Y.C., E.Z.S., G.L., U.B.T., P.M.R., D.C., N.S., S.M., K.L.F., B.M.P., T.M., S.P., J.C.M.W., D.M.R., A.G.U., F.R., B.M., M.S., A.B.N., Y.L., M.H.G., O.M., B.H.C.S., S.B.F., A.A., D.D., D.I.C., S.R.H., E.J.B., G.S., S.C., A.C., D.L., J.R. and V.G. Statistical analysis was performed by K.L.L., N.L.G., M.D.R., A.V.S., D.E.A., M.M.-N., B.P.K., J.C.B., J.G.S., M.F.S., K.L., J.D., K.M.R., R.W.D., U.V., G.L., L.M.R., Y.L. and D.I.C. Funding was obtained by P.T.E., C.M.A., M.K.C., J.G.S., N.L.S., J.D.S., J.I.R., L.J.L., T.B.H., H.V., A.H., E.B., U.B.T., P.M.R., B.M.P., T.M., H.-E.W., J.C.M.W., D.M.R., A.G.U., Y.L., O.M., B.H.C.S., S.B.F., A.A., D.D., S.R.H., E.J.B., V.G. and S. Kääb. Study supervision was performed by P.T.E., K.L.L., C.M.A., M.K.C., N.L.S., J.I.R., A.H., P.M.R., B.M.P., J.C.M.W., A.G.U., Y.L., B.H.C.S., S.B.F., S.R.H., E.J.B., V.G. and S. Kääb., P.T.E., K.L.L., C.M.A., N.L.G., M.D.R., A.V.S., D.E.A., M.M.-N., B.P.K., J.C.B., M.K.C., M.D., K.O., T. Tanaka, B.H.C.S., S.B.F., A.A., D.D., J.B., D.I.C., S.R.H., V.G., E.J.B. and S. Kääb had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
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Ellinor, P., Lunetta, K., Albert, C. et al. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet 44, 670–675 (2012). https://doi.org/10.1038/ng.2261
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DOI: https://doi.org/10.1038/ng.2261
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