Evaluation of genetic variants related to lipid levels among the North Indian population.

A heavy burden of cardiometabolic conditions on low- and middle-income countries like India that are rapidly undergoing urbanization remains unaddressed. Indians are known to have high levels of triglycerides and low levels of HDL-C along with moderately higher levels of LDL-C. The genome-wide findings from Western populations need to be validated in an Indian context for a better understanding of the underlying etiology of dyslipidemia in India. We aim to validate 12 genetic variants associated with lipid levels among rural and urban Indian populations and derive unweighted and weighted genetic risk scores (uGRS and wGRS) for lipid levels among the Indian population. Assuming an additive model of inheritance, linear regression models adjusted for all the possible covariates were run to examine the association between 12 genetic variants and total cholesterol, triglycerides, HDL-C, LDL-C, and VLDL-C among 2,117 rural and urban Indian participants. The combined effect of validated loci was estimated by allelic risk scores, unweighted and weighted by their effect sizes. The wGRS for triglycerides and VLDL-C was derived based on five associated variants (rs174546 at , rs17482753 at , rs2293889 at , rs4148005 at , and rs4420638 at ), which was associated with 36.31 mg/dL of elevated triglyceride and VLDL-C levels ( = 0.95, SE = 0.16, < 0.001). Similarly, every unit of combined risk score (rs2293889 at and rs4147536 at ) was associated with 40.62 mg/dL of higher total cholesterol ( = 1.01, SE = 0.23, < 0.001) and 33.97 mg/dL of higher LDL-C ( = 1.03, SE = 0.19, < 0.001) based on its wGRS (rs2293889 at , rs4147536 at , rs4420638 at , and rs660240 at ). The wGRS derived from five associated variants (rs174546 at , rs17482753 at , rs4148005 at , rs4420638 at , and rs7832643 at ) was associated with 10.64 mg/dL of lower HDL-C ( = -0.87, SE = 0.14, < 0.001). We confirm the role of eight genome-wide association study (GWAS) loci related to different lipid levels in the Indian population and demonstrate the combined effect of variants for lipid traits among Indians by deriving the polygenic risk scores. Similar studies among different populations are required to validate the GWAS loci and effect modification of these loci by lifestyle and environmental factors related to urbanization.