Genome-wide association study of PR interval.

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.

• Authors: Arne Pfeufer, Charlotte van Noord, Kristin D Marciante, Dan E Arking, Martin G Larson, Albert Vernon Smith, Kirill V Tarasov, Martina Müller, Nona Sotoodehnia, Moritz F Sinner, Germaine C Verwoert, Man Li, W H Linda Kao, Anna Köttgen, Josef Coresh, Joshua C Bis, Bruce M Psaty, Kenneth Rice, Jerome I Rotter, Fernando Rivadeneira, Albert Hofman, Jan A Kors, Bruno H C Stricker, André G Uitterlinden, Cornelia M van Duijn, Britt M Beckmann, Wiebke Sauter, Christian Gieger, Steven A Lubitz, Christopher Newton-Cheh, Thomas J Wang, Jared W Magnani, Renate B Schnabel, Mina K Chung, John Barnard, Jonathan D Smith, David R Van Wagoner, Ramachandran S Vasan, Thor Aspelund, Gudny Eiriksdottir, Tamara B Harris, Lenore J Launer, Samer S Najjar, Edward Lakatta, David Schlessinger, Manuela Uda, Gonçalo R Abecasis, Bertram Müller-Myhsok, Georg B Ehret, Eric Boerwinkle, Aravinda Chakravarti, Elsayed Z Soliman, Kathryn L Lunetta, Siegfried Perz, H-Erich Wichmann, Thomas Meitinger, Daniel Levy, Vilmundur Gudnason, Patrick T Ellinor, Serena Sanna, Stefan Kääb, Jacqueline C M Witteman, Alvaro Alonso, Emelia J Benjamin, Susan R Heckbert
• Journal: Nature genetics (Nat Genet) Vol. 42 Issue 2 Pg. 153-9 (Feb 2010) ISSN: 1546-1718 [Electronic] United States
• PMID: 20062060 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Topics

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