Nature 448, 353-357 (19 July 2007) | doi:10.1038/nature06007; Received 6 April 2007; Accepted 11 June 2007; Published online 1 July 2007

Variants conferring risk of atrial fibrillation on chromosome 4q25

Daniel F. Gudbjartsson1, David O. Arnar2, Anna Helgadottir1, Solveig Gretarsdottir1, Hilma Holm2, Asgeir Sigurdsson1, Adalbjorg Jonasdottir1, Adam Baker1, Gudmar Thorleifsson1, Kristleifur Kristjansson1, Arnar Palsson1, Thorarinn Blondal1, Patrick Sulem1, Valgerdur M. Backman1, Gudmundur A. Hardarson1, Ebba Palsdottir1, Agnar Helgason1, Runa Sigurjonsdottir2, Jon T. Sverrisson3, Konstantinos Kostulas4, Maggie C. Y. Ng5, Larry Baum5, Wing Yee So5, Ka Sing Wong5, Juliana C. N. Chan5, Karen L. Furie6, Steven M. Greenberg6, Michelle Sale6, Peter Kelly6, Calum A. MacRae7, Eric E. Smith6, Jonathan Rosand6, Jan Hillert4, Ronald C. W. Ma5, Patrick T. Ellinor7, Gudmundur Thorgeirsson2, Jeffrey R. Gulcher1, Augustine Kong1, Unnur Thorsteinsdottir1 & Kari Stefansson1

  1. deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland
  2. Division of Cardiology, Department of Medicine, Landspitali University Hospital, 101 Reykjavik, Iceland
  3. Department of Medicine, Akureyri Regional Hospital, 600 Akureyri, Iceland
  4. Department of Neurology, Karolinska Institutet at Karolinska University Hospital, Huddinge S-141 86, Sweden
  5. Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong
  6. Department of Neurology,
  7. Cardiology Division and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA

Correspondence to: Daniel F. Gudbjartsson1Kari Stefansson1 Correspondence and requests for materials should be addressed to D.F.G. (Email: daniel.gudbjartsson@decode.is) or K.S. (Email: kstefans@decode.is).

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans and is characterized by chaotic electrical activity of the atria1. It affects one in ten individuals over the age of 80 years, causes significant morbidity and is an independent predictor of mortality2. Recent studies have provided evidence of a genetic contribution to AF3, 4, 5. Mutations in potassium-channel genes have been associated with familial AF6, 7, 8, 9, 10 but account for only a small fraction of all cases of AF11, 12. We have performed a genome-wide association scan, followed by replication studies in three populations of European descent and a Chinese population from Hong Kong and find a strong association between two sequence variants on chromosome 4q25 and AF. Here we show that about 35% of individuals of European descent have at least one of the variants and that the risk of AF increases by 1.72 and 1.39 per copy. The association with the stronger variant is replicated in the Chinese population, where it is carried by 75% of individuals and the risk of AF is increased by 1.42 per copy. A stronger association was observed in individuals with typical atrial flutter. Both variants are adjacent to PITX2, which is known to have a critical function in left–right asymmetry of the heart13, 14, 15.

Extra navigation