Scientific Publications

The Impact of Ancestry and Common Genetic Variants on QT Interval in African Americans.

Publication TypeJournal Article
AuthorsSmith, 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 WC, 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 ZM, Post WS, Zonderman AB, Taylor HA, Murray SS, Ferrucci L., Arking DE, Evans MK, Fox ER, Sotoodehnia N., Heckbert SR, Whitsel EA, and Newton-Cheh C.
AbstractBACKGROUND: -Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death (SCD) 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 seven population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from electrocardiograms. Second, imputation was performed for 2.8 million SNPs and a genome-wide association (GWA) study of QT interval performed in ten cohorts (n=13 105). There was no evidence of association between genetic ancestry and QT interval (p=0.94). Genome-wide significant associations (p<2.5x10(-8)) were identified with SNPs at two loci, upstream of the genes NOS1AP (rs12143842, p=2x10(-15)) and ATP1B1 (rs1320976, p=2x10(-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 p-values (p<10(-5)) were observed for SNPs at several other loci previously identified in GWA 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 ancestry. In addition, our GWA study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include African Americans.
Year of Publication2012
JournalCirculation. Cardiovascular genetics
Date Published (YYYY/MM/DD)2012/11/19
ISSN Number1942-325X