Impact of ancestry and common genetic variants on QT interval in African Americans.

Circ Cardiovasc Genet
Authors
J Gustav Smith
Christy Avery
Daniel Evans
Michael Nalls
Yan Meng
Erin Smith
Cameron Palmer
Toshiko Tanaka
Reena Mehra
Anne Butler
Taylor Young
Sarah Buxbaum
Kathleen Kerr
Gerald Berenson
Renate Schnabel
Guo Li
Patrick Ellinor
Jared Magnani
Wei Chen
Joshua Bis
J David Curb
Wen-Chi Hsueh
Jerome Rotter
Yongmei Liu
Anne Newman
Marian Limacher
Kari North
Alexander Reiner
P Miguel Quibrera
Nicholas Schork
Andrew Singleton
Bruce Psaty
Elsayed Soliman
Allen Solomon
Sathanur Srinivasan
Alvaro Alonso
Robert Wallace
Susan Redline
Zhu-Ming Zhang
Wendy Post
Alan Zonderman
Herman Taylor
Sarah Murray
Luigi Ferrucci
Dan Arking
Michele Evans
Ervin Fox
Nona Sotoodehnia
Susan Heckbert
Eric Whitsel
Christopher Newton-Cheh
CARe and COGENT consortia
Keywords
Female
Humans
Male
Adult
Aged
Middle Aged
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Genetic Variation
European Continental Ancestry Group
Genome, Human
African Americans
Electrocardiography
Genealogy and Heraldry
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

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.
Year of Publication
2012
Journal
Circ Cardiovasc Genet
Volume
5
Issue
6
Pages
647-55
Date Published
2012 Dec
ISSN
1942-3268
URL
http://circgenetics.ahajournals.org/cgi/pmidlookup?view=long&pmid=23166209
DOI
10.1161/CIRCGENETICS.112.962787
PubMed ID
23166209
PubMed Central ID
PMC3568265
Links
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M01-RR00425 / RR / NCRR NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
R00 HL098458 / HL / NHLBI NIH HHS / United States
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N01-HC-95162 / HC / NHLBI NIH HHS / United States
R01 HL075366 / HL / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
R03 HD062783 / HD / NICHD NIH HHS / United States
N01WH42129-32 / WH / WHI NIH HHS / United States
1-R01-ES017794 / ES / NIEHS NIH HHS / United States
R01 HL046380 / HL / NHLBI NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
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U01 HL080295 / HL / NHLBI NIH HHS / United States
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