Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population

Dan Arking, Amit Khera, Chao Xing, W. H Linda Kao, Wendy S Post, Eric Boerwinkle, Aravinda Chakravarti

Research output: Contribution to journalArticle

Abstract

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6 x 10-5) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP 6 sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63 x 10-8), as well as the sex-interaction with rs16847548 (P = 8.68 x 10-6). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P

Original languageEnglish (US)
Article numbere4333
JournalPLoS One
Volume4
Issue number1
DOIs
StatePublished - Jan 30 2009

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Single Nucleotide Polymorphism
Sudden Cardiac Death
Hispanic Americans
Population
ancestry
Health
death
gender
cohort studies
etiology
Cohort Studies
heart
loci
sampling
Direction compound

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population. / Arking, Dan; Khera, Amit; Xing, Chao; Kao, W. H Linda; Post, Wendy S; Boerwinkle, Eric; Chakravarti, Aravinda.

In: PLoS One, Vol. 4, No. 1, e4333, 30.01.2009.

Research output: Contribution to journalArticle

Arking, Dan ; Khera, Amit ; Xing, Chao ; Kao, W. H Linda ; Post, Wendy S ; Boerwinkle, Eric ; Chakravarti, Aravinda. / Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population. In: PLoS One. 2009 ; Vol. 4, No. 1.
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