Open Access Research

Evaluation of seven common lipid associated loci in a large Indian sib pair study

Sajjad Rafiq19*, Kranthi Kumar M Venkata2, Vipin Gupta3, DG Vinay2, Charles J Spurgeon2, Smitha Parameshwaran2, Sandeep N Madana2, Sanjay Kinra1, Liza Bowen1, Nicholas J Timpson45, George Davey Smith5, Frank Dudbridge16, Dorairaj Prabhakaran378, Yoav Ben-Shlomo45, K Srinath Reddy8, Shah Ebrahim13, Giriraj R Chandak2 and Indian Migration Study Group

Author Affiliations

1 Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK

2 Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Habshiguda, Uppal Road, Hyderabad, 500007, India

3 South Asia Network for Chronic Disease, Public Health Foundation of India, C-1/52, Safdarjung Development Area, New Delhi, 110016, India

4 School of Social and Community Medicine, University of Bristol, Bristol, UK

5 MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK

6 Bloomsbury Centre for Genetic Epidemiology and Statistics, London, UK

7 Centre for Chronic Disease Control, New Delhi, India

8 Public Health Foundation of India, New Delhi, India

9 Genetic Epidemiology and Bioinformatics Research Group, Human Genetics Research Division, University of Southampton, School of Medicine, Southampton General Hospital, Hants, UK

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Lipids in Health and Disease 2012, 11:155  doi:10.1186/1476-511X-11-155

Published: 14 November 2012

Abstract

Background

Genome wide association studies (GWAS), mostly in Europeans have identified several common variants as associated with key lipid traits. Replication of these genetic effects in South Asian populations is important since it would suggest wider relevance for these findings. Given the rising prevalence of metabolic disorders and heart disease in the Indian sub-continent, these studies could be of future clinical relevance.

Methods

We studied seven common variants associated with a variety of lipid traits in previous GWASs. The study sample comprised of 3178 sib-pairs recruited as participants for the Indian Migration Study (IMS). Associations with various lipid parameters and quantitative traits were analyzed using the Fulker genetic association model.

Results

We replicated five of the 7 main effect associations with p-values ranging from 0.03 to 1.97x10-7. We identified particularly strong association signals at rs662799 in APOA5 (beta=0.18 s.d, p=1.97 x 10-7), rs10503669 in LPL (beta =−0.18 s.d, p=1.0 x 10-4) and rs780094 in GCKR (beta=0.11 s.d, p=0.001) loci in relation to triglycerides. In addition, the GCKR variant was also associated with total cholesterol (beta=0.11 s.d, p=3.9x10-4). We also replicated the association of rs562338 in APOB (p=0.03) and rs4775041 in LIPC (p=0.007) with LDL-cholesterol and HDL-cholesterol respectively.

Conclusions

We report associations of five loci with various lipid traits with the effect size consistent with the same reported in Europeans. These results indicate an overlap of genetic effects pertaining to lipid traits across the European and Indian populations.

Keywords:
SNP; Fulker’s Association model and Lipid traits