Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese.
Clara Sze Man TangHe ZhangChloe Y Y CheungMing XuJenny C Y HoWei ZhouStacey Shawn ChernyYan ZhangOddgeir HolmenKa-Wing AuHaiyi YuLin XuJia JiaRobert M PorschLijie SunWeixian XuHuiping ZhengLai-Yung WongYiming MuJingtao DouCarol H Y FongShuyu WangXueyu HongLiguang DongYanhua LiaoJiansong WangLevina S M LamXi SuHua YanMin-Lee YangJin ChenChung-Wah SiuGaoqiang XieYu-Cho WooYangfeng WuKathryn C B TanKristian HveemBernard M Y CheungSebastian ZöllnerAimin XuY Eugene ChenChao Qiang JiangYouyi ZhangTai-Hing LamSanthi K GaneshYong HuoPak C ShamKaren S L LamCristen J WillerHung-Fat TseWei GaoPublished in: Nature communications (2015)
Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.69 × 10(-7)), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci-PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser-also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2, is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association (P<0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD.
Keyphrases
- copy number
- genome wide
- coronary artery disease
- dna methylation
- fatty acid
- cardiovascular disease
- percutaneous coronary intervention
- gene expression
- intellectual disability
- autism spectrum disorder
- genome wide association study
- acute coronary syndrome
- heart failure
- aortic valve
- transcription factor
- left ventricular
- data analysis
- single cell