TY - JOUR T1 - Impact of ancestry and common genetic variants on QT interval in African Americans. JF - Circ Cardiovasc Genet Y1 - 2012 A1 - Smith, J Gustav A1 - Avery, Christy L A1 - Evans, Daniel S A1 - Nalls, Michael A A1 - Meng, Yan A A1 - Smith, Erin N A1 - Palmer, Cameron A1 - Tanaka, Toshiko A1 - Mehra, Reena A1 - Butler, Anne M A1 - Young, Taylor A1 - Buxbaum, Sarah G A1 - Kerr, Kathleen F A1 - Berenson, Gerald S A1 - Schnabel, Renate B A1 - Li, Guo A1 - Ellinor, Patrick T A1 - Magnani, Jared W A1 - Chen, Wei A1 - Bis, Joshua C A1 - Curb, J David A1 - Hsueh, Wen-Chi A1 - Rotter, Jerome I A1 - Liu, Yongmei A1 - Newman, Anne B A1 - Limacher, Marian C A1 - North, Kari E A1 - Reiner, Alexander P A1 - Quibrera, P Miguel A1 - Schork, Nicholas J A1 - Singleton, Andrew B A1 - Psaty, Bruce M A1 - Soliman, Elsayed Z A1 - Solomon, Allen J A1 - Srinivasan, Sathanur R A1 - Alonso, Alvaro A1 - Wallace, Robert A1 - Redline, Susan A1 - Zhang, Zhu-Ming A1 - Post, Wendy S A1 - Zonderman, Alan B A1 - Taylor, Herman A A1 - Murray, Sarah S A1 - Ferrucci, Luigi A1 - Arking, Dan E A1 - Evans, Michele K A1 - Fox, Ervin R A1 - Sotoodehnia, Nona A1 - Heckbert, Susan R A1 - Whitsel, Eric A A1 - Newton-Cheh, Christopher KW - Adult KW - African Americans KW - Aged KW - Electrocardiography KW - European Continental Ancestry Group KW - Female KW - Genealogy and Heraldry KW - Genetic Variation KW - Genome, Human KW - Genome-Wide Association Study KW - Humans KW - Male KW - Middle Aged KW - Polymorphism, Single Nucleotide AB -

BACKGROUND: Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval.

METHODS AND RESULTS: First, individual estimates of African and European ancestry were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7 population-based cohorts of African Americans (n=12,097) and regressed on measured QT interval from ECGs. Second, imputation was performed for 2.8 million SNPs, and a genome-wide association study of QT interval was performed in 10 cohorts (n=13,105). There was no evidence of association between genetic ancestry and QT interval (P=0.94). Genome-wide significant associations (P<2.5 × 10(-8)) were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842, P=2 × 10(-15)) and ATP1B1 (rs1320976, P=2 × 10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low probability values (P<10(-5)) were observed for SNPs at several other loci previously identified in genome-wide association studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF, and PLN.

CONCLUSIONS: We observed no difference in duration of cardiac repolarization with global genetic indices of African American ancestry. In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry.

VL - 5 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23166209?dopt=Abstract ER -