Common Single-Nucleotide Polymorphisms Act in Concert to Affect Plasma Levels of High-Density Lipoprotein Cholesterol

Genetics Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
The American Journal of Human Genetics (Impact Factor: 10.93). 11/2007; 81(6):1298-303. DOI: 10.1086/522497
Source: PubMed


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.

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Available from: Alexander Pertsemlidis, Oct 01, 2015
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    • "based on the following criteria: HapMap-CEU dataset, r 2 ≥ 0.8 for each bin, minor allele frequency ≥1%, and a 4–10 kB margin from gene boundary . Additional SNPs were added based on published genome-wide association studies for associations with HDL-C and TG [11] [12] [13] [14]. A total of 350 SNPs to be tested for therapy response were selected, and 34 SNPs with inter-ethnic difference in allele frequencies were added to aid in correcting for potential population stratification within the European-American population [15]. "
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