Journal
CIRCULATION-CARDIOVASCULAR GENETICS
Volume 5, Issue 6, Pages 647-655Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.112.962787
Keywords
electrocardiography; electrophysiology; genome-wide association studies; ion channels; repolarization
Funding
- National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]
- Cleveland Family Study: Case Western Reserve University (National Institutes of Health [NIH]) [HL 46380, M01RR00080]
- Jackson Heart Study: Jackson State University [N01-HC-95170]
- University of Mississippi [N01-HC-95171]
- Tougaloo College by the NHLBI [N01-HC-95172]
- National Center for Minority Health and Health Disparities
- Multi-Ethnic Study of Atherosclerosis: University of Washington [N01-HC-95159]
- Regents of the University of California [N01-HC-95160]
- Columbia University [N01-HC-95161]
- Johns Hopkins University [N01-HC-95162, N01-HC-95168]
- University of Minnesota [N01-HC-95163]
- Northwestern University [N01-HC-95164]
- Wake Forest University [N01-HC-95165]
- University of Vermont [N01-HC-95166]
- New England Medical Center [N01-HC-95167]
- Harbor-UCLA Research and Education Institute [N01-HC-95169]
- Cedars-Sinai Medical Center [R01-HL-071205]
- NIH, National Institute on Aging (NIA)
- NIA [AG-023629, AG-15928, AG-20098, AG-027058, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]
- National Center for Research Resources [M01-RR00425]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]
- NIH [HHSN268200782096C, R01-HL-111089, R01-HL-088456, 1R01HL098283]
- NIH, NIA
- National Center for Minority Health and Health Disparities, NIH
- National Center on Minority Health and Health Disparities [Z01-AG000513]
- NHLBI, NIH, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]
- NHLBI [N02-HL-64278, R00-HL-098458]
- Swedish Heart Lung Foundation
- NIH/National Institute of Environmental Health Sciences [1-R01-ES017794]
- NIH/ National Cancer Institute [N01-WH-2-2110]
- Doris Duke Charitable Foundation
- Burroughs Wellcome Fund Career Award for Medical Scientists
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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<2.5x10(-8)) were identified with SNPs at 2 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 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 Afr. (Circ Cardiovasc Genet. 2013;5:647-655.)
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