Newly identified loci that influence lipid concentrations and risk of coronary artery disease – Source: Nature Genetics, online Jan 13, 2008

[Note: LDL has been termed “bad” cholesterol and HDL “good” cholesterol. Together with triglycerides and Lp(a) cholesterol – a genetic variation of LDL – they make up the total blood cholesterol count.]

To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals.

Overall, we identify strongly associated variants:

  • In eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9)

  • And also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol;

  • Near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol;

  • Near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides;

  • And a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol).

  • Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls. [Additionally, “we did not find that variants influencing your good cholesterol (HDL) were associated with decreased risk of coronary artery disease,” according to study co-director Goncalo Abecasis.]

    Source: Nature Genetics. Online Jan 13, 2008. DOI:10.1038/ng.76, by Abecasis GR, Mohlke KL,et al. Department of Genetics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA. [E-mail:]

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