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The Impact of Ancestry and Common Genetic Variants on QT Interval in African Americans.

Author:
  • Gustav Smith
  • Christy L Avery
  • Daniel S Evans
  • Michael A Nalls
  • Yan A Meng
  • Erin N Smith
  • Cameron Palmer
  • Toshiko Tanaka
  • Reena Mehra
  • Anne M Butler
  • Taylor Young
  • Sarah G Buxbaum
  • Kathleen F Kerr
  • Gerald S Berenson
  • Renate B Schnabel
  • Li Jun Guo
  • Patrick T Ellinor
  • Jared W Magnani
  • Wei Chen
  • Joshua C Bis
  • J David Curb
  • Wen-Chi Hsueh
  • Jerome I Rotter
  • Yongmei Liu
  • Anne B Newman
  • Marian C Limacher
  • Kari E North
  • Alexander P Reiner
  • P Miguel Quibrera
  • Nicholas J Schork
  • Andrew B Singleton
  • Bruce M Psaty
  • Elsayed Z Soliman
  • Allen J Solomon
  • Sathanur R Srinivasan
  • Alvaro Alonso
  • Robert Wallace
  • Susan Redline
  • Zhu-Ming Zhang
  • Wendy S Post
  • Alan B Zonderman
  • Herman A Taylor
  • Sarah S Murray
  • Luigi Ferrucci
  • Dan E Arking
  • Michele K Evans
  • Ervin R Fox
  • Nona Sotoodehnia
  • Susan R Heckbert
  • Eric A Whitsel
  • Christopher Newton-Cheh
Publishing year: 2012
Language: English
Pages: 647-655
Publication/Series: Circulation: Cardiovascular Genetics
Volume: 5
Issue: 6
Document type: Journal article
Publisher: American Heart Association

Abstract english

BACKGROUND: -Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death (SCD) 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 seven population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from electrocardiograms. Second, imputation was performed for 2.8 million SNPs and a genome-wide association (GWA) study of QT interval performed in ten 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 two 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 p-values (p<10(-5)) were observed for SNPs at several other loci previously identified in GWA 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 ancestry. In addition, our GWA study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include African Americans.

Keywords

  • Cardiac and Cardiovascular Systems
  • electrophysiology
  • electrocardiography
  • genome-wide association studies
  • ion channels
  • repolarization

Other

Published
  • ISSN: 1942-325X
E-mail: gustav [dot] smith [at] med [dot] lu [dot] se

Associate professor

Cardiology

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D1232C

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Cardiovascular Epigenetics

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Heart Failure and Mechanical Support

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Molecular Epidemiology and Cardiology

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