Association of common genetic variants with lipid traits in the Indian population

• Published in: PloS one 2014-07, Vol.9 (7), p.e101688-e101688
• Main Authors: Walia, Gagandeep Kaur, Gupta, Vipin, Aggarwal, Aastha, Asghar, Mohammad, Dudbridge, Frank, Timpson, Nicholas, Singh, Nongmaithem Suraj, Kumar, M Ravi, Kinra, Sanjay, Prabhakaran, Dorairaj, Reddy, K Srinath, Chandak, Giriraj Ratan, Smith, George Davey, Ebrahim, Shah
• Format: Article
• Language: English
• Subjects: Adult; Biology and Life Sciences; Cardiovascular disease; Cholesterol; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Chromosomes; Chronic illnesses; Exercise; Female; Gender; Genetic diversity; Genetic variance; Genome-Wide Association Study - methods; Genomes; Genomics; Heritability; High density lipoprotein; Humans; India - ethnology; Lipid Metabolism; Lipids; Loci; Low density lipoprotein; Low density lipoproteins; Male; Middle Aged; Physical activity; Polymorphism, Single Nucleotide; Population studies; Populations; Quantitative genetics; Quantitative Trait Loci; Sex; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Strong interactions (field theory); Triglycerides; Triglycerides - blood; Urban areas; Urban Population; Urbanization; Whites - genetics; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0101688

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.