title: Common single-nucleotide polymorphisms act in concert to affect plasma levels of high-density lipoprotein cholesterol.
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.
authors.affiliation: Genetics Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Spirin
authors.forename: Steffen
authors.initials: S
authors.lastname: Schmidt
authors.forename: Alexander
authors.initials: A
authors.lastname: Pertsemlidis
authors.forename: Richard S
authors.initials: RS
authors.lastname: Cooper
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Cohen
authors.forename: Shamil R
authors.initials: SR
authors.lastname: Sunyaev
mesh_terms: D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL