Genetics
GWAS replication confirms CETP rs3764261 association with HDL-C in a 3,781-person Asian Indian cohort (PLoS One 2012)
Original title: A replication study of GWAS-derived lipid genes in Asian Indians: the chromosomal region 11q23.3 harbors loci contributing to triglycerides
Researchers attempted to replicate six GWAS-identified lipid loci in a non-European population, the Sikh Diabetes Study cohort of 3,781 Asian Indians (2,902 from Punjab, 879 from the US). The study confirmed a strong association of CETP rs3764261 with HDL cholesterol (p = 2.03x10-26), one of only two loci that showed convincing replication; the other, BUD13-ZNF259 rs964184, was associated with triglycerides (p = 1.74x10-17). Extending the analysis to 45 SNPs across the 11q23.3 region (BUD13-ZNF259, APOA5-A4-C3-A1, SIK3) in 8,530 Asian Indians from the LOLIPOP and SDS cohorts, five additional SNPs showed significant triglyceride associations, though the strongest signal remained BUD13-ZNF259 rs964184 (p = 1.06x10-39). The authors conclude these validated loci, including CETP, warrant further sequencing and functional study for their relevance to dyslipidemia and diabetes-related cardiovascular risk.
Original abstract
Recent genome-wide association scans (GWAS) and meta-analysis studies on European populations have identified many genes previously implicated in lipid regulation. Validation of these loci on different global populations is important in determining their clinical relevance, particularly for development of novel drug targets for treating and preventing diabetic dyslipidemia and coronary artery disease (CAD). In an attempt to replicate GWAS findings on a non-European sample, we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638) in our Asian Indian cohort from the Sikh Diabetes Study (SDS) comprising 3,781 individuals (2,902 from Punjab and 879 from the US). Two of the six SNPs examined showed convincing replication in these populations of Asian Indian origin. Our study confirmed a strong association of CETP rs3764261 with high-density lipoprotein cholesterol (HDL-C) (p = 2.03×10(-26)). Our results also showed significant associations of two GWAS SNPs (rs964184 and rs12286037) from BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG) levels in this Asian Indian cohort (rs964184: p = 1.74×10(-17); rs12286037: p = 1.58×10(-2)). We further explored 45 SNPs in a ∼195 kb region within the chromosomal region 11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes) in 8,530 Asian Indians from the London Life Sciences Population (LOLIPOP) (UK) and SDS cohorts. Five more SNPs revealed significant associations with TG in both cohorts individually as well as in a joint meta-analysis. However, the strongest signal for TG remained with BUD13-ZNF259 (rs964184: p = 1.06×10(-39)). Future targeted deep sequencing and functional studies should enhance our understanding of the clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG) and, consequently, diabetes and CAD.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.