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Common variants at ten loci influence QT interval duration in the QTGEN Study.

TitleCommon variants at ten loci influence QT interval duration in the QTGEN Study.
Publication TypeJournal Article
Year of Publication2009
AuthorsNewton-Cheh, C, Eijgelsheim, M, Rice, KM, de Bakker, PIW, Yin, X, Estrada, K, Bis, JC, Marciante, K, Rivadeneira, F, Noseworthy, PA, Sotoodehnia, N, Smith, NL, Rotter, JI, Kors, JA, Witteman, JCM, Hofman, A, Heckbert, SR, O'Donnell, CJ, Uitterlinden, AG, Psaty, BM, Lumley, T, Larson, MG, Stricker, BHCh
JournalNat Genet
Volume41
Issue4
Pagination399-406
Date Published2009 Apr
ISSN1546-1718
KeywordsAdaptor Proteins, Signal Transducing, Adult, Aged, Arrhythmias, Cardiac, Chromosome Mapping, Death, Sudden, Cardiac, Electroencephalography, ERG1 Potassium Channel, Ether-A-Go-Go Potassium Channels, European Continental Ancestry Group, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Humans, KCNQ1 Potassium Channel, Meta-Analysis as Topic, Muscle Proteins, NAV1.5 Voltage-Gated Sodium Channel, Polymorphism, Single Nucleotide, Potassium Channels, Voltage-Gated, Risk Factors, Sodium Channels
Abstract<p>QT interval duration, reflecting myocardial repolarization on the electrocardiogram, is a heritable risk factor for sudden cardiac death and drug-induced arrhythmias. We conducted a meta-analysis of three genome-wide association studies in 13,685 individuals of European ancestry from the Framingham Heart Study, the Rotterdam Study and the Cardiovascular Health Study, as part of the QTGEN consortium. We observed associations at P < 5 x 10(-8) with variants in NOS1AP, KCNQ1, KCNE1, KCNH2 and SCN5A, known to be involved in myocardial repolarization and mendelian long-QT syndromes. Associations were found at five newly identified loci, including 16q21 near NDRG4 and GINS3, 6q22 near PLN, 1p36 near RNF207, 16p13 near LITAF and 17q12 near LIG3 and RFFL. Collectively, the 14 independent variants at these 10 loci explain 5.4-6.5% of the variation in QT interval. These results, together with an accompanying paper, offer insights into myocardial repolarization and suggest candidate genes that could predispose to sudden cardiac death and drug-induced arrhythmias.</p>
DOI10.1038/ng.364
Alternate JournalNat Genet
PubMed ID19305408
PubMed Central IDPMC2701449
Grant ListN01-HC-25195 / HC / NHLBI NIH HHS / United States
P30 DK063491-05 / DK / NIDDK NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
K23 HL080025-04 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
P30 DK063491-039004 / DK / NIDDK NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
K23-HL-080025 / HL / NHLBI NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
M01 RR00069 / RR / NCRR NIH HHS / United States
P30 DK063491-029004 / DK / NIDDK NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
P30 DK063491-019004 / DK / NIDDK NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
P30 DK063491-049004 / DK / NIDDK NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N02-HL-64278 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
K23 HL080025 / HL / NHLBI NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States