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Biological, clinical and population relevance of 95 loci for blood lipids
 

Summary: ARTICLES
Biological, clinical and population
relevance of 95 loci for blood lipids
A list of authors and their affiliations appears at the end of the paper.
Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and
triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic
intervention. We screened the genome for common variants associated with plasma lipids in .100,000 individuals of
European ancestry. Here we report 95 significantly associated loci (P , 5 3 1028
), with 59 showing genome-wide significant
association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms
(SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously
implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme
lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African
Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally,
we validated three of the novel genes--GALNT2, PPP1R3B and TTC39B--with experiments in mouse models. Taken together,
our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify
new therapeutic opportunities for the prevention of CAD.
Plasma concentrations of total cholesterol (TC), low-density lipo-
protein cholesterol (LDL-C), high-density lipoprotein cholesterol
(HDL-C) and triglycerides (TG) are heritable risk factors for cardio-

  

Source: Abecasis, Goncalo - Department of Biostatistics, University of Michigan

 

Collections: Biology and Medicine; Mathematics