Impact of ancestry and common genetic variants on QT interval in African Americans.
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.
Smith, JG; Avery, CL; Evans, DS; Nalls, MA; Meng, YA; Smith, EN; Palmer, C; Tanaka, T; Mehra, R; Butler, AM; Young, T; Buxbaum, SG; Kerr, KF; Berenson, GS; Schnabel, RB; Li, G; Ellinor, PT; Magnani, JW; Chen, W; Bis, JC; Curb, JD; Hsueh, W-C; Rotter, JI; Liu, Y; Newman, AB; Limacher, MC; North, KE; Reiner, AP; Quibrera, PM; Schork, NJ; Singleton, AB; Psaty, BM; Soliman, EZ; Solomon, AJ; Srinivasan, SR; Alonso, A; Wallace, R; Redline, S; Zhang, Z-M; Post, WS; Zonderman, AB; Taylor, HA; Murray, SS; Ferrucci, L; Arking, DE; Evans, MK; Fox, ER; Sotoodehnia, N; Heckbert, SR; Whitsel, EA; Newton-Cheh, C; CARe and COGENT consortia,
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