Common Variants at Ten Loci Influence QT Interval Duration in the QTGEN Study

Overview

Journal Nat Genet

Specialty Genetics

Date 2009 Mar 24

PMID 19305408

Citations 223

Authors

Christopher Newton-Cheh

Mark Eijgelsheim

Kenneth M Rice

Paul I W de Bakker

Xiaoyan Yin

Karol Estrada

Joshua C Bis

Kristin Marciante

Fernando Rivadeneira

Peter A Noseworthy

Nona Sotoodehnia

Nicholas L Smith

Jerome I Rotter

Jan A Kors

Jacqueline C M Witteman

Albert Hofman

Susan R Heckbert

Christopher J ODonnell

Andre G Uitterlinden

Bruce M Psaty

Thomas Lumley

Martin G Larson

Bruno H Ch Stricker

Affiliations

Soon will be listed here.

Abstract

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.

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