Abstract

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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Acknowledgements

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.

Author information

Author notes

    • Daniel F Gudbjartsson
    •  & Hilma Holm

    These authors contributed equally to this work.

Affiliations

  1. DeCode Genetics, Reykjavik, Iceland.

    • Daniel F Gudbjartsson
    • , Hilma Holm
    • , Solveig Gretarsdottir
    • , Gudmar Thorleifsson
    • , G Bragi Walters
    • , Jeffrey Gulcher
    • , Augustine Kong
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson
  2. Department of Internal Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA.

    • Hilma Holm
  3. Department of Internal Medicine, Division of Cardiology, Landspitali University Hospital, Reykjavik, Iceland.

    • Gudmundur Thorgeirsson
    •  & David O Arnar
  4. University of Iceland, Faculty of Medicine, Reykjavik, Iceland.

    • Gudmundur Thorgeirsson
    • , David O Arnar
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson
  5. Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.

    • Ellisiv B Mathiesen
  6. Department of Neurology, University Hospital of North Norway, Tromsø, Norway.

    • Ellisiv B Mathiesen
  7. Institute of Community Medicine, University of Tromsø, Tromsø, Norway.

    • Inger Njølstad
    • , Audhild Nyrnes
    • , Tom Wilsgaard
    •  & Maja-Lisa Løchen
  8. Department of Geriatrics, University Hospital of North Norway, Tromsø, Norway.

    • Audhild Nyrnes
  9. Department of Cardiology, University Hospital of North Norway, Tromsø, Norway.

    • Erin M Hald
    •  & Maja-Lisa Løchen
  10. Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.

    • Kristian Hveem
  11. Norwegian Institute of Public Health, Oslo, Norway.

    • Camilla Stoltenberg
  12. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

    • Gayle Kucera
    • , Tanya Stubblefield
    • , Shannon Carter
    • , Dan Roden
    •  & Dawood Darbar
  13. Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong.

    • Maggie C Y Ng
    • , Larry Baum
    • , Wing Yee So
    • , Ka Sing Wong
    • , Juliana C N Chan
    •  & Ronald C W Ma
  14. Institute of Epidemiology, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Neuherberg, Germany.

    • Christian Gieger
    •  & H-Erich Wichmann
  15. Department of Neurology, Klinikum of Grosshadern, Ludwig Maximilians University Munich, Munich, Germany.

    • Andreas Gschwendtner
    •  & Martin Dichgans
  16. Institute of Experimental Medicine, Molecular Neurobiology, University of Kiel, Kiel, Germany.

    • Gregor Kuhlenbäumer
  17. Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany.

    • Klaus Berger
  18. Department of Neurology and Leibniz Institute for Atherosclerosis Research, University of Muenster, Muenster, Germany.

    • E Bernd Ringelstein
  19. Clinical Neuroscience, St. George's University of London, London, UK.

    • Steve Bevan
    •  & Hugh S Markus
  20. Department of Neurology, Karolinska University Hospital Huddinge, Stockholm, Sweden.

    • Konstantinos Kostulas
    •  & Jan Hillert
  21. Department of Neurology, Landspitali University Hospital, Reykjavik, Iceland.

    • Sigurlaug Sveinbjörnsdóttir
    •  & Einar M Valdimarsson

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Contributions

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.

Competing interests

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

Corresponding authors

Correspondence to Daniel F Gudbjartsson or Kari Stefansson.

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    Supplementary Text and Figures

    Supplementary Figures 1–2, Supplementary Tables 1–3 and Supplementary Methods

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DOI

https://doi.org/10.1038/ng.417

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