We aimed to validate the GWAS loci (identified in European populations) related to serum lipid levels (total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and very low-density lipoprotein cholesterol (VLDL-C)) in the Indian population originally recruited to examine the 20-year trend of cardiometabolic risk factors in rural and urban areas around National Capital region in India. Isolated DNA was processed for genotyping of 12 established GWAS variants using multiplex Sequenom Mass ARRAY technology. We examined the association of these genetic variants with different lipid levels and found association of eight variants for lipid levels. We also derived weighted genetic risk scores (wGRAS) using the validated variants. The wGRS for triglycerides and VLDL-C was derived based on four associated variants (rs174546 at <a href="https://www.ncbi.nlm.nih.gov/gene/3992">FADS1</a>, rs17482753 at <a href="https://www.ncbi.nlm.nih.gov/gene/4023">LPL</a>, rs2293889 at <a href="https://www.ncbi.nlm.nih.gov/gene/7227">TRPS1</a>, rs4148005 at <a href="https://www.ncbi.nlm.nih.gov/gene/10351">ABCA8</a>, rs4420638 at <a href="https://www.ncbi.nlm.nih.gov/gene/341">APOC1</a>) which was associated with 36.31 mg/dL elevated triglycerides and VLDL-C (β=0.95, SE=0.16, p&#x3C;0.001). Similarly, every unit of combined risk score (rs2293889 at TRPS1 and rs4147536 at <a href="https://www.ncbi.nlm.nih.gov/gene/125">ADH1B</a>) was associated with 40.62 mg/dL higher total cholesterol (β=1.01, SE=0.23, p&#x3C;0.001) and 33.97 mg/dL higher LDL-C (β= 1.03, SE =0.19, p&#x3C;0.001) based on its wGRS (rs2293889 at TRPS1, rs4147536 at ADH1B, rs4420638 at APOC1 and rs660240 at <a href="https://www.ncbi.nlm.nih.gov/gene/1952">CELSR2</a>). The wGRS derived from five associated variants (rs174546 and FADS1, rs17482753 at LPL, rs4148005 at ABCA8, rs4420638 at APOC1 and rs7832643 at <a href="https://www.ncbi.nlm.nih.gov/gene/5339">PLEC</a>) was associated with 10.64 mg/dL lower HDL-C (β= -0.87, SE =0.14, p&#x3C;0.001). Therefore, we confirm the role of eight 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 weighted genetic risk scores.The phenotypic and genotypic data will be made available on the dbGaP portal for access.

Genetic Markers of Lipids in Indians: A Validation Study of Most Relevant Findings of Genome-Wide Association Studies

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