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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.

SUBMITTER: Pfeufer A 

PROVIDER: S-EPMC2850197 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Genome-wide association study of PR interval.

Pfeufer Arne A   van Noord Charlotte C   Marciante Kristin D KD   Arking Dan E DE   Larson Martin G MG   Smith Albert Vernon AV   Tarasov Kirill V KV   Müller Martina M   Sotoodehnia Nona N   Sinner Moritz F MF   Verwoert Germaine C GC   Li Man M   Kao W H Linda WH   Köttgen Anna A   Coresh Josef J   Bis Joshua C JC   Psaty Bruce M BM   Rice Kenneth K   Rotter Jerome I JI   Rivadeneira Fernando F   Hofman Albert A   Kors Jan A JA   Stricker Bruno H C BH   Uitterlinden André G AG   van Duijn Cornelia M CM   Beckmann Britt M BM   Sauter Wiebke W   Gieger Christian C   Lubitz Steven A SA   Newton-Cheh Christopher C   Wang Thomas J TJ   Magnani Jared W JW   Schnabel Renate B RB   Chung Mina K MK   Barnard John J   Smith Jonathan D JD   Van Wagoner David R DR   Vasan Ramachandran S RS   Aspelund Thor T   Eiriksdottir Gudny G   Harris Tamara B TB   Launer Lenore J LJ   Najjar Samer S SS   Lakatta Edward E   Schlessinger David D   Uda Manuela M   Abecasis Gonçalo R GR   Müller-Myhsok Bertram B   Ehret Georg B GB   Boerwinkle Eric E   Chakravarti Aravinda A   Soliman Elsayed Z EZ   Lunetta Kathryn L KL   Perz Siegfried S   Wichmann H-Erich HE   Meitinger Thomas T   Levy Daniel D   Gudnason Vilmundur V   Ellinor Patrick T PT   Sanna Serena S   Kääb Stefan S   Witteman Jacqueline C M JC   Alonso Alvaro A   Benjamin Emelia J EJ   Heckbert Susan R SR  

Nature genetics 20100110 2


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 ind  ...[more]

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