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Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry

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Abstract

We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio RR = 1.19; P = 2.3 × 10−7). We replicated this association in an independent cohort from the German AF Network (odds ratio = 1.44; P = 1.6 × 10−11; combined RR = 1.25; combined P = 1.8 × 10−15).

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Figure 1: Regional association plots for signal loci on chromosome 16.

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  • 29 July 2009

    NOTE: In the version of this article initially published online, the name of author H.-Erich Wichmann was incorrectly given as Hans-E. Wichmann and this author's affiliation at the Institute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians University, Munich, Germany, was missing. The error has been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

Complete study acknowledgments are listed in the Supplementary Note. The authors thank the studies' participants, staff and the funding agencies for their support.

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Contributions

Statistical analyses: K.M.R., D.E.A., A.P., C.V.N., A.V.S., A.D., R.B.D., T.L., G.B.E., T.A., M.L., K.W., A.K., C.M.v.D., K.L.L. and M.M. Informatics: A.V.S., T.A., K.L.L. and M.M. Data preparation: T.A., K.W., A.C., K.L.L., V.G. and S.P. Sample collection and phenotype data collection: E.J.B., C.V.N., A.V.S., R.B.S., E.B., M.F.S., J.H., E.Z.S., T.J.W., G.E., D.L., B.M.P., A.M.C., A.H., R.S.V., S.K.A., P.A.W., S.R.H., V.G., A.A., S.K., T.M., S.P., G.S. and H.-E.W. Genotyping: A.V.S., M.F.S., T.A., G.E., J.I.R., V.G. and T.M.; Manuscript writing: E.J.B., K.M.R., D.E.A., S.A.L., K.L.L. and V.G. Review and revision of the manuscript: E.J.B., K.M.R., D.E.A., A.P., C.V.N., A.V.S., R.B.S., J.C.B., E.B., A.D., S.A.L., T.L., G.B.E., J.H., T.A., C.N.-C., M.G.L., K.D.M., E.Z.S., F.R., T.J.W., G.E., D.L., B.M.P., A.M.C., A.H., R.S.V., T.B.H., J.I.R., W.H.L.K., B.H.C.S., L.J.L., N.L.S., A.C., A.G.U., N.S., A.K., C.M.v.D., K.L.L., S.R.H., V.G., A.A., S.K., P.T.E., J.C.M.W., T.M., M.M., S.P., G.S. and H.-E.W. Intellectual input: E.J.B., K.M.R., D.E.A., R.B.S., M.G.L., K.L.L., S.R.H., S.K., P.T.E. and J.C.M.W. Study design: E.J.B., K.M.R., D.E.A., A.P., C.V.N., T.L., M.G.L., G.E., B.M.P., A.H., R.S.V., T.B.H., B.H.C.S., L.J.L., A.G.U., N.S., K.L.L., S.R.H., S.K., P.T.E., J.C.M.W., T.M., M.M., S.P., G.S. and H.-E.W. Study interpretation: E.J.B., K.M.R., C.V.N., R.B.S., J.C.B., E.B., T.L., R.S.V., W.H.L.K., K.L.L., S.R.H., A.A., S.K. and P.T.E. Study coordination: E.J.B., J.C.B., G.E., S.R.H., S.K. and P.T.E. Obtaining study funding: E.J.B., A.P., E.B., B.M.P., T.B.H., L.J.L., P.A.W., V.G., S.K., P.T.E., T.M., G.S. and H.-E.W.

Corresponding authors

Correspondence to Emelia J Benjamin or Jacqueline C M Witteman.

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Competing interests

Aravinda Chakravarti is a paid member of the Scientific Advisory Board of Affymetrix, a role that is managed by the Committee on Conflict of Interest of the Johns Hopkins University School of Medicine.

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Supplementary Figures 1–4, Supplementary Tables 1–4, Supplementary Note and Supplementary Methods (PDF 412 kb)

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Benjamin, E., Rice, K., Arking, D. et al. Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. Nat Genet 41, 879–881 (2009). https://doi.org/10.1038/ng.416

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