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Nature Research, Nature Genetics, 2(42), p. 153-159, 2010

DOI: 10.1038/ng.517

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Genome-wide association study of PR interval

Journal article published in 2010 by Arne Pfeufer, Charlotte van Noord, Kristin D. Marciante, Dan E. Arking, Martin G. Larson ORCID, Av Smith, Albert Vernon Smith ORCID, Kirill V. Tarasov, Martina Müller, Nona Sotoodehnia, Moritz F. Sinner, Germaine C. Verwoert, Man Li, Wh H. Linda Kao, W. H. Linda Kao and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.