title: 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.
authors.affiliation: South Asia Network for Chronic Disease (SANCD), Public Health Foundation of India (PHFI), New Delhi, India.
authors.forename: Gagandeep Kaur
authors.initials: GK
authors.lastname: Walia
authors.affiliation: Department of Anthropology, University of Delhi, Delhi, India.
authors.forename: Vipin
authors.initials: V
authors.lastname: Gupta
authors.affiliation: South Asia Network for Chronic Disease (SANCD), Public Health Foundation of India (PHFI), New Delhi, India.
authors.forename: Aastha
authors.initials: A
authors.lastname: Aggarwal
authors.affiliation: Department of Anthropology, Rajiv Gandhi University, Itanagar, Arunachal Pradesh, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Asghar
authors.affiliation: Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Frank
authors.initials: F
authors.lastname: Dudbridge
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Timpson
authors.affiliation: Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.
authors.forename: Nongmaithem Suraj
authors.initials: NS
authors.lastname: Singh
authors.affiliation: Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.
authors.forename: M Ravi
authors.initials: MR
authors.lastname: Kumar
authors.affiliation: Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kinra
authors.affiliation: Centre for Chronic Disease Control, New Delhi, India; Public Health Foundation of India, New Delhi, India.
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.affiliation: Public Health Foundation of India, New Delhi, India.
authors.forename: K Srinath
authors.initials: KS
authors.lastname: Reddy
authors.affiliation: Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.
authors.forename: Giriraj Ratan
authors.initials: GR
authors.lastname: Chandak
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.affiliation: South Asia Network for Chronic Disease (SANCD), Public Health Foundation of India (PHFI), New Delhi, India; Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Shah
authors.initials: S
authors.lastname: Ebrahim
mesh_terms: D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D007194:India / Q000208:ethnology; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D014280:Triglycerides / Q000097:blood; D014505:Urban Population; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides