Common single-nucleotide polymorphisms act in concert to affect plasma levels of high-density lipoprotein cholesterol

Victor Spirin, Steffen Schmidt, Alexander Pertsemlidis, Richard S. Cooper, Jonathan C. Cohen, Shamil R. Sunyaev

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

The identification of DNA sequence variants underlying human complex phenotypes remains a significant challenge for several reasons: individual variants can have small phenotypic effects or low population frequencies, and multiple allelic variants may act in concert to affect a trait. We evaluated the combined effect of allelic variants in seven genes involved in high-density lipoprotein (HDL) metabolism, using forward stepwise regression. Analysis of all known common single-nucleotide polymorphisms (SNPs) in the seven candidate genes revealed four variants that were associated with incremental changes in HDL cholesterol levels in three independent samples. Conversely, analysis of 660 polymorphisms in eight genes that do not appear to be involved in HDL metabolism did not identify any associations with plasma HDL-cholesterol levels. These data indicate that several common SNPs act in concert to influence plasma levels of HDL cholesterol.

Original languageEnglish (US)
Pages (from-to)1298-1303
Number of pages6
JournalAmerican Journal of Human Genetics
Volume81
Issue number6
DOIs
StatePublished - 2007

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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