Genetics
A genome-wide meta-analysis in Hispanic populations confirms CETP as a genome-wide-significant locus for HDL cholesterol (Sci Rep 2016)
Original title: Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs
Performing a genome-wide meta-analysis of lipid traits in 4,383 individuals of Mexican and Mexican American ancestry, followed up in three additional Hispanic samples totaling 7,876 more individuals, researchers found genome-wide significant signals for HDL cholesterol at LPL, ABCA1, ZNF259/APOA5, LIPC, and CETP, alongside distinct loci for total cholesterol, LDL cholesterol, and triglycerides. Lead SNPs from the European Global Lipids Genetics Consortium showed strong concordance in direction and magnitude of effect in the Hispanic samples, and combining the European and Hispanic datasets identified five additional novel genome-wide-significant regions. The findings validate CETP's HDL cholesterol association across a previously underrepresented Hispanic ancestry population, alongside tissue-specific enrichment of gene-expression signals at the top lipid-associated loci.
Original abstract
We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.