A genome wide association study identifies common variants associated with lipid levels in the Chinese population

PLoS One. 2013 Dec 30;8(12):e82420. doi: 10.1371/journal.pone.0082420. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • China
  • Cohort Studies
  • Female
  • Genetic Markers
  • Genetic Variation*
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Lipid Metabolism / genetics*
  • Lipids / blood
  • Male
  • Middle Aged

Substances

  • Genetic Markers
  • Lipids

Grant support

This work was supported by grants from the National Basic Research Program grant (2011CB503806), the Program of Introducing Talents of Discipline to Universities and Yangze Scholarship to TW, the General Program of the National Natural Science Foundation of China (30945204, 30360124, 30260110, 81172751 and 81202274), the Guangxi Provincial Department of Finance and Education (2009GJCJ150), intramural funding from Fudan-VARI (Van Andel Institute, United States of America) Center for Genetic Epidemiology and Intramural Funding from Fudan University Institute of Urology to ZM and Program for New Century Excellent Talents in University to MH. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.