Genome-wide association study of PR interval.

Pfeufer A, van Noord C, Marciante KD, Arking DE, Larson MG, Smith AV, Tarasov KV, Muller M, Sotoodehnia N, Sinner MF, Verwoert GC, Li M, Kao WH, Kottgen A, Coresh J, Bis JC, Psaty BM, Rice K, Rotter JI, Rivadeneira F, Hofman A, Kors JA, Stricker BH, Uitterlinden AG, van Duijn CM, Beckmann BM, Sauter W, Gieger C, Lubitz SA, Newton-Cheh C, Wang TJ, Magnani JW, Schnabel RB, Chung MK, Barnard J, Smith JD, Van Wagoner DR, Vasan RS, Aspelund T, Eiriksdottir G, Harris TB, Launer LJ, Najjar SS, Lakatta E, Schlessinger D, Uda M, Abecasis GR, Muller-Myhsok B, Ehret GB, Boerwinkle E, Chakravarti A, Soliman EZ, Lunetta KL, Perz S, Wichmann HE, Meitinger T, Levy D, Gudnason V, Ellinor PT, Sanna S, Kaab S, Witteman JC, Alonso A, Benjamin EJ and Heckbert SR

Nat Genet (2010) 42:153-9

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.