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A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke


We expanded our genome-wide association study on atrial fibrillation (AF) in Iceland, which previously identified risk variants on 4q25, and tested the most significant associations in samples from Iceland, Norway and the United States. A variant in the ZFHX3 gene on chromosome 16q22, rs7193343-T, associated significantly with AF (odds ratio OR = 1.21, P = 1.4 × 10−10). This variant also associated with ischemic stroke (OR = 1.11, P = 0.00054) and cardioembolic stroke (OR = 1.22, P = 0.00021) in a combined analysis of five stroke samples.

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This project was supported by US National Institutes of Health grants HL075266 and U01 HL65962 and American Heart Association grant 0940116N. Case ascertainment in the West Germany region (Westphalia) was part of the German Competence Net Stroke, which was supported by the German Federal Ministry of Education and Research (01GI9909/3). In the Dortmund Health Study (controls, West Germany) blood collection was done through funds of the Institute of Epidemiology and Social Medicine University of Muenster, the collection of sociodemographic and clinical variables was supported by the German Migraine & Headache Society (DMKG) and by unrestricted grants of equal share from Astra Zeneca, Berlin Chemie, Boots Healthcare, Glaxo-Smith-Kline, McNeil Pharma, MSD Sharp & Dohme and Pfizer to the University of Muenster.

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The study was designed and results interpreted by D.F.G., H.H., D.O.A., S.G., G.B.W., J.G., U.T. and K.S. The first draft was written by D.F.G., H.H., D.O.A., S.G., U.T. and K.S. Statistical analysis: D.F.G., G. Thorleifsson, A.K. Collection of Icelandic data: D.O.A., H.H., G. Thorgeirsson, E.M.V. and S.S. Collection of Norwegian AF data: M.-L.L., C.S., E.B.M., I.N., A.N., T.W., E.M.H. and K.H. Collection of United States AF data: D.D., G. Kucera, T.S., S.C. and D.R. Collection of Hong Kong AF data: M.C.Y.N., L.B., W.Y.S., K.S.W., J.C.N.C. and R.C.W.M. Collection of Swedish stroke data: J.H. and K.K. Collection of German stroke data: C.G., H.-E.W., A.G., M.D., G. Kuhlenbäumer, K.B. and E.B.R. Collection of UK stroke data: H.S.M. and S.B. All authors contributed to the final version of the paper.

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Correspondence to Daniel F Gudbjartsson or Kari Stefansson.

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The authors from DeCode Genetics own stock and stock options in the company.

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Gudbjartsson, D., Holm, H., Gretarsdottir, S. et al. A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. Nat Genet 41, 876–878 (2009).

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