Newly identified loci that influence lipid concentrations and risk of coronary artery disease – Source: Nature Genetics, online Jan 13, 2008
by Goncalo R Abecasis and Karen L Mohlke, et al.
ProHealthNetwork.com
01-13-2008
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[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: goncalo@umich.edu]
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