Association of Common Genetic Variants with Lipid Traits in the Indian Population

Abstract

Genome-wide association studies (GWAS) have been instrumental in identifying novel genetic variants associated with altered plasma lipid levels. However, these quantitative trait loci have not been tested in the Indian population, where there is a poorly understood and growing burden of cardiometabolic disorders. We present the association of six single nucleotide polymorphisms in 1671 sib pairs (3342 subjects) with four lipid traits: total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). We also investigated the interaction effects of gender, location, fat intake and physical activity. Each copy of the risk allele of rs964184 at APOA1 was associated with 1.06 mmol/l increase in triglycerides (SE = 0.049; p = 0.006), rs3764261 at CETP with 1.02 mmol/l increase in both total cholesterol (SE = 0.042; p = 0.017) and HDL-C (SE = 0.041; p = 0.008), rs646776 at CELSR2-PSRC1-SORT1 with 0.96 mmol/l decrease in cholesterol (SE = 0.043; p = 0.0003) and 0.15 mmol/l decrease in LDL-C levels (SE = 0.043; p = 0.0003) and rs2954029 at TRIB1 with 1.02 mmol/l increase in HDL-C (SE = 0.039; p = 0.047). A combined risk score of APOA1 and CETP loci predicted an increase of 1.25 mmol/l in HDL-C level (SE = 0.312; p = 0.0007). Urban location and sex had strong interaction effects on the genetic association of most of the studied loci with lipid traits. To conclude, we validated four genetic variants (identified by GWAS in western populations) associated with lipid traits in the Indian population. The interaction effects found here may explain the sex-specific differences in lipid levels and their heritability. Urbanization appears to influence the nature of the association with GWAS lipid loci in this population. However, these findings will require replication in other Indian populations.

Quantitative trait loci at the 11q23.3 chromosomal region related to dyslipidemia in the population of Andhra Pradesh, India

“…Another study on western Indians found 3238C > G (rs5128) and -1131 T > C (rs662799) that belong to APOC3 and APOA5 genes, respectively, as associated with elevated levels of triglycerides and VLDLs [19]. Further, the most replicated GWAS variant rs964184 that wasidentified as associated with elevated triglycerides among Indians [10, 11] is also not evident in our study. The association of the variants of the regulatory genes with abnormal lipid traits is very much established among Caucasians [20] and has been replicated among other populations such as Chinese [21] and Japanese [22].…”

Medical genetics and genomic medicine in India: current status and opportunities ahead

“…; Walia et al. ). Pharmacogenomics is also an important area of work of many scientists (Senapati et al.…”

“…The Department of Medical Genetics at SGPGIMS, Lucknow also holds a 2 week long program every year for clinicians. It is aimed at nichamy et al 2004;Dhandapany et al 2009;Ronsard et al 2014;Sharma et al 2014;Singh et al 2014;Talwar et al 2014;Walia et al 2014). Pharmacogenomics is also an important area of work of many scientists (Senapati et al 2014).…”

A common variant association study in ethnic Saudi Arabs reveals novel susceptibility loci for hypertriglyceridemia

“…The encoded LAMC1 protein is thought to mediate the attachment, migration and organization of cells into tissue during embryonic development as a result of its interaction with other cellular matrix components. Similarly, the TRIB1 which harbors the rs6982502 is involved in the regulation of hepatic lipogenesis, and has also been associated with plasma TG levels, ischemic heart disease (IHD) and familial hypercholesterolemia (59)(60)(61)(62). Currently, there is no data in the literature pertaining to the role of either this SNP or the encoding LAMC1 gene in cardiovascular disease.…”