A Genome Wide Association Study Identifies Common Variants Associated with Lipid Levels in the Chinese Population

Li Zhou,Tangchun Wu,Zengnan Mo,Xinwen Min,Huan Guo,Meian He,Yong Gao,Dongfeng Li,Dianke Yu,Chen Wu,Xiaobo Yang,Jing Yuan,Suli Huang,Youjie Wang,Huaixing Li,Xiayun Dai,Handong Yang,Mingjian Lang,Qifei Deng,S Lilly Zheng,Yuan Liang,Wen Tan,Jingwen Zhu,Weihong Chen,Kan Zhai,Xue Qin,Jianfeng Xu,Haiying Zhang,Aihua Tan,Xu Lin,Jiang Chang,Feng Wang,Sheng Wei,Xiaomin Zhang,Frank B Hu,Yiqin Wang,Jielin Sun,Dafeng Lin,Xiaoping Miao,Jiang Zhu,Weili Fang ,Ying He ,Dong Lin

doi:10.1371/journal.pone.0082420

Abstract

Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52×10-16, 1.38×10-6 and 5.59×10-9, respectively). These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population.

Highlights

Plasma lipid levels are well-established risk factors for cardiovascular disease [1,2,3]
A genome wide association studies (GWAS) conducted in a Japanese population for lipid traits replicated 6 loci that were associated with high-density lipoprotein cholesterol (HDL) and TG levels [7]
We carried out two GWAS on four lipid traits total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL) and HDL in the DFTJ-cohort (1,452 subjects) and the Fangchenggang Area Male Health and Examination Survey (FAMHES) (1,999 subjects) and meta-analysis of these two GWAS

Summary

Introduction

Plasma lipid levels are well-established risk factors for cardiovascular disease [1,2,3]. Recent genome wide association studies (GWAS) have identified several loci and single nucleotide polymorphisms (SNPs) that are associated with lipid levels in European populations [4,5,6]. A GWAS conducted in a Japanese population for lipid traits replicated 6 loci (including CETP, LIPC, APOA5 cluster, LPL, GCKR and DOCK7-ANGPTL3) that were associated with HDL and TG levels [7]. Their comparison with reports from GWAS in European populations provided evidence that the genetic variation has different magnitudes of effect in the different ethnicities. Further work is required to confirm the lipid-associated loci and their effects, in other ethnic populations

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Methods

Conclusion