Journal article
Impact of Ancestry and Common Genetic Variants on QT Interval in African Americans
Circulation. Cardiovascular genetics, Vol.5(6), pp.647-655
12/01/2012
DOI: 10.1161/CIRCGENETICS.112.962787
PMCID: PMC3568265
PMID: 23166209
Abstract
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.)
Details
- Title: Subtitle
- Impact of Ancestry and Common Genetic Variants on QT Interval in African Americans
- Creators
- J. Gustav Smith - Massachusetts Institute of TechnologyChristy L. Avery - University of North Carolina at Chapel HillDaniel S. Evans - California Pacific Medical CenterMichael A. NallsYan A. Meng - Massachusetts Institute of TechnologyErin N. Smith - University of California San DiegoCameron Palmer - Massachusetts Institute of TechnologyToshiko Tanaka - National Institutes of HealthReena Mehra - Case Western Reserve UniversityAnne M. Butler - University of North Carolina at Chapel HillTaylor Young - Massachusetts Institute of TechnologySarah G. Buxbaum - Jackson State UniversityKathleen F. Kerr - University of WashingtonGerald S. Berenson - Tulane UniversityRenate B. SchnabelGuo Li - University of WashingtonPatrick T. Ellinor - Harvard UniversityJared W. Magnani - Boston UniversityWei Chen - Tulane UniversityJoshua C. Bis - University of WashingtonJ. David Curb - University of Hawaiʻi at MānoaWen-Chi Hsueh - University of California, San FranciscoJerome I. Rotter - Cedars-Sinai Medical CenterYongmei Liu - Wake Forest UniversityAnne B. Newman - University of PittsburghMarian C. Limacher - University of FloridaKari E. North - University of North Carolina at Chapel HillAlexander P. Reiner - University of WashingtonP. Miguel Quibrera - University of North Carolina at Chapel HillNicholas J. Schork - Scripps Research InstituteAndrew B. Singleton - National Institutes of HealthBruce M. Psaty - University of WashingtonElsayed Z. Soliman - Wake Forest UniversityAllen J. Solomon - George Washington UniversitySathanur R. Srinivasan - Tulane UniversityAlvaro Alonso - University of MinnesotaRobert Wallace - University of IowaSusan Redline - Harvard UniversityZhu-Ming Zhang - Wake Forest UniversityWendy S. Post - Johns Hopkins UniversityAlan B. Zonderman - National Institutes of HealthHerman A. Taylor - University of MississippiSarah S. Murray - Scripps Research InstituteLuigi Ferrucci - National Institutes of HealthDan E. Arking - Johns Hopkins UniversityMichele K. Evans - National Institutes of HealthErvin R. Fox - University of MississippiNona Sotoodehnia - University of WashingtonSusan R. Heckbert - University of WashingtonEric A. Whitsel - University of North Carolina at Chapel HillChristopher Newton-Cheh - Massachusetts Institute of TechnologyCARe & COGENT Consortia
- Resource Type
- Journal article
- Publication Details
- Circulation. Cardiovascular genetics, Vol.5(6), pp.647-655
- DOI
- 10.1161/CIRCGENETICS.112.962787
- PMID
- 23166209
- PMCID
- PMC3568265
- NLM abbreviation
- Circ Cardiovasc Genet
- ISSN
- 1942-325X
- eISSN
- 1942-3268
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 9
- Grant note
- N01-HC-95164 / Northwestern University HL 46380; M01RR00080 / Cleveland Family Study: Case Western Reserve University (National Institutes of Health [NIH]) AG-023629; AG-15928; AG-20098; AG-027058; N01AG62101; N01AG62103; N01AG62106; 1R01AG032098-01A1 / NIA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) N01-HC-95162; N01-HC-95168 / Johns Hopkins University 1-R01-ES017794 / NIH/National Institute of Environmental Health Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) HHSN268200782096C; R01-HL-111089; R01-HL-088456; 1R01HL098283 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA N01-HC-95171 / University of Mississippi UL1TR000124 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) N01WH022110 / WOMEN'S HEALTH INITIATIVE - OFFICE OF THE DIRECTOR NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA N01HC085082 / DIVISION OF EPIDEMIOLOGY AND CLINICAL APPLICATIONS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) R01ES017794 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) National Center for Minority Health and Health Disparities, NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Minority Health & Health Disparities (NIMHD) R01AG023629 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) P30DK063491 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) N01-HC-95166 / University of Vermont NIH, NIA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) National Center for Minority Health and Health Disparities; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Minority Health & Health Disparities (NIMHD) N01-HC-95172 / Tougaloo College by the NHLBI N01-HC-95160 / Regents of the University of California; University of California System DK063491 / National Institute of Diabetes and Digestive and Kidney Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) NIH, National Institute on Aging (NIA); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) N01-HC-95167 / New England Medical Center Burroughs Wellcome Fund Career Award for Medical Scientists; Burroughs Wellcome Fund P20MD006899 / National Institute on Minority Health and Health Disparities; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Minority Health & Health Disparities (NIMHD) Z01-AG000513 / National Center on Minority Health and Health Disparities; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Minority Health & Health Disparities (NIMHD) UL1RR025774 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) N01WH22110; 24152; 32100-2; 32105-6; 32108-9; 32111-13; 32115; 32118-32119; 32122; 42107-26; 42129-32; 44221 / NHLBI, NIH, US Department of Health and Human Services N01-HC-95159 / Multi-Ethnic Study of Atherosclerosis: University of Washington Swedish Heart Lung Foundation; Swedish Heart-Lung Foundation N01-WH-2-2110 / NIH/ National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R03HD061437 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) N01-HC-95161 / Columbia University R13HL095166 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01-HL-071205 / Cedars-Sinai Medical Center N01-HC-95165 / Wake Forest University T32CA009330 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) M01-RR00425 / National Center for Research Resources; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) Doris Duke Charitable Foundation; Doris Duke Charitable Foundation (DDCF) N01-HC-95169 / Harbor-UCLA Research and Education Institute HHSN268201100005C; HHSN268201100006C; HHSN268201100007C; HHSN268201100008C; HHSN268201100009C; HHSN268201100010C; HHSN268201100011C; HHSN268201100012C / National Heart, Lung, and Blood Institute (NHLBI); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) N01-HC-95170 / Jackson Heart Study: Jackson State University N01-HC-95163 / University of Minnesota; University of Minnesota System N02-HL-64278; R00-HL-098458 / NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 12/01/2012
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984363577702771
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