Association of SCARB1 variants with subclinical atherosclerosis and incident cardiovascular disease: The multi-ethnic study of atherosclerosis

Ani Manichaikul, Adam C. Naj, David Herrington, Wendy Post, Stephen S. Rich, Annabelle Rodriguez

Research output: Contribution to journalArticle

Abstract

Objective-We previously reported a statistically significant association of SCARB1 intronic single nucleotide polymorphism (SNP) rs10846744 with common carotid intimal-medial artery thickness in each of the 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups (white, Chinese, black, and Hispanic). Methods and Results-Using an expanded sample of 7936 Multi-Ethnic Study of Atherosclerosis participants, phenotyped for measures of subclinical atherosclerosis, incident myocardial infarction, and cardiovascular disease, and genotyped through the SNP Health Association Resource project, we have now examined the genetic association of these phenotypes with 126 genotyped and imputed SCARB1 SNPs. We also performed stratified analyses to examine whether SCARB1 SNP effects differed by sex. Our analysis of the full Multi-Ethnic Study of Atherosclerosis cohort provides strong evidence for the association of rs10846744 with common carotid intimal-medial thickness (P=1.04E-4 in combined analysis of all 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups). In sex-stratified analysis, we observed statistically significant association of rs10846744 with incident cardiovascular disease events in males (P=0.01). Examining analytical results from the Myocardial Infarction Genetics Consortium for replication, we observed further support for the association of rs10846744 with myocardial infarction. Conclusion-The SCARB1 SNP, rs10846744, exerts a major effect on subclinical atherosclerosis and incident cardiovascular disease in humans.

Original languageEnglish (US)
Pages (from-to)1991-1999
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Volume32
Issue number8
DOIs
StatePublished - Aug 1 2012

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Keywords

  • cardiovascular disease
  • genetics
  • genomics
  • lipids

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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