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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.

Original publication

DOI

10.1038/ng.517

Type

Journal article

Journal

Nature genetics

Publication Date

02/2010

Volume

42

Pages

153 - 159

Addresses

Institute of Human Genetics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. arne.pfeufer@web.de

Keywords

Heart Conduction System, Humans, Atrial Fibrillation, Genetic Predisposition to Disease, Electrocardiography, Cohort Studies, Aged, Female, Male, Meta-Analysis as Topic, Genome-Wide Association Study, Genetic Loci