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ABSTRACT 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

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS SEQUENCING IN OVER 50,000 CASES IDENTIFIES CODING AND STRUCTURAL VARIATION UNDERLYING ATRIAL FIBRILLATION RISK Article 06

March 2025 RARE GENETIC VARIANTS INVOLVED IN INCREASED RISK OF PAROXYSMAL ATRIAL FIBRILLATION IN A JAPANESE POPULATION Article Open access 17 April 2025 META-ANALYSIS OF GENOME-WIDE

ASSOCIATIONS AND POLYGENIC RISK PREDICTION FOR ATRIAL FIBRILLATION IN MORE THAN 180,000 CASES Article 06 March 2025 REFERENCES * Go, A. S. et al. Prevalence of diagnosed atrial fibrillation

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  Google Scholar  Download references ACKNOWLEDGEMENTS We thank the patients and their family members whose contribution made this work possible; the nurses at Noatun (deCODE’s sample

recruitment center), personnel at the deCODE core facilities, and M. Shea for the ongoing enrolment of patients at Massachusetts General Hospital; and A. Plourde and S. Makino for technical

assistance. AUTHOR CONTRIBUTIONS D.F.G., D.O.A., A.H., S.G., P.T.E., J.R. U.T. and K.S. wrote the first draft of the paper. D.O.A., H.H., R.S., J.T.S. and G.T. collected and diagnosed the

Icelandic AF samples. Ko.K. and J.H. collected and diagnosed the Swedish samples. K.L.F., S.M.G., M.S., P.K., C.A.M., E.E.S., J.R. and P.T.E. collected and diagnosed the US samples.

M.C.Y.N., L.B., W.Y.S., K.S.W., J.C.N.C. and R.C.W.M collected and diagnosed the Hong Kong samples. A.H., S.G., A.S., A.J., A.B., T.B., V.M.B., G.A.H. and E.P. performed genotyping and

experimental work. D.F.G., G.T., A.P., P.S., A.H. and A.K. analyzed the data. D.F.G., D.O.A., A.H., S.G., Kr.K., J.R., J.H., R.C.W.M., P.T.E, G.T, J.R.G., A.K., U.T. and K.S. planned,

supervised and coordinated the work. All authors contributed to the final version of the paper. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * deCODE genetics, Sturlugata 8, 101 Reykjavik,

Iceland, Daniel F. Gudbjartsson, Anna Helgadottir, Solveig Gretarsdottir, Asgeir Sigurdsson, Adalbjorg Jonasdottir, Adam Baker, Gudmar Thorleifsson, Kristleifur Kristjansson, Arnar Palsson, 

Thorarinn Blondal, Patrick Sulem, Valgerdur M. Backman, Gudmundur A. Hardarson, Ebba Palsdottir, Agnar Helgason, Jeffrey R. Gulcher, Augustine Kong, Unnur Thorsteinsdottir & Kari

Stefansson * Division of Cardiology, Department of Medicine, Landspitali University Hospital, 101 Reykjavik, Iceland, David O. Arnar, Hilma Holm, Runa Sigurjonsdottir & Gudmundur

Thorgeirsson * Department of Medicine, Akureyri Regional Hospital, 600 Akureyri, Iceland, Jon T. Sverrisson * Department of Neurology, Karolinska Institutet at Karolinska University

Hospital, Huddinge S-141 86, Sweden, Konstantinos Kostulas & Jan Hillert * Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin,

Hong Kong, Maggie C. Y. Ng, Larry Baum, Wing Yee So, Ka Sing Wong, Juliana C. N. Chan & Ronald C. W. Ma * Department of Neurology,, Karen L. Furie, Steven M. Greenberg, Michelle Sale, 

Peter Kelly, Eric E. Smith & Jonathan Rosand * Cardiology Division and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

02114, USA, Calum A. MacRae & Patrick T. Ellinor Authors * Daniel F. Gudbjartsson View author publications You can also search for this author inPubMed Google Scholar * David O. Arnar

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* Kari Stefansson View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to Daniel F. Gudbjartsson or Kari Stefansson.

ETHICS DECLARATIONS COMPETING INTERESTS Some of the authors own stock and/or stock options in deCODE genetics, Inc. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION This file contains

Supplementary Methods, Supplementary Tables 1-9, Supplementary Figures 1-4 and additional references. (PDF 612 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE

THIS ARTICLE Gudbjartsson, D., Arnar, D., Helgadottir, A. _et al._ Variants conferring risk of atrial fibrillation on chromosome 4q25. _Nature_ 448, 353–357 (2007).

https://doi.org/10.1038/nature06007 Download citation * Received: 06 April 2007 * Accepted: 11 June 2007 * Published: 01 July 2007 * Issue Date: 19 July 2007 * DOI:

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