Genetics
Genome-wide meta-analysis of 20,000-plus people confirms CETP among eleven established lipid loci and finds new ones (Nat Genet 2008)
Original title: Newly identified loci that influence lipid concentrations and risk of coronary artery disease
Combining genotype-imputed meta-analysis across three genome-wide scans totaling 8,816 individuals, then following up promising signals in 11,569 additional individuals, this study identified strongly associated variants at eleven loci previously implicated in lipid metabolism, including ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG, and PCSK9. It also identified several newly discovered loci: near MVK-MMAB and GALNT2 (primarily HDL cholesterol), near SORT1 (primarily LDL cholesterol), near TRIB1, MLXIPL, and ANGPTL3 (primarily triglycerides), and a multi-gene locus near NCAN (both triglycerides and LDL cholesterol). The eleven independent LDL-cholesterol-raising variants identified were also more frequent in coronary artery disease cases than controls.
Original abstract
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.
geneticsHDL biologyLDL and apoB
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.