Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese

• DOI: 10.1038/ncomms10206
• Publication Date: 2015-12-22T10:03:39Z
• Authors: Clara S. Tang; He Zhang; Chloe Y. Y. Cheung; Ming Xu; Jenny C. Y. Ho; Wei Zhou; Stacey S. Cherny; Yan Zhang; Oddgeir Holmen; Ka-Wing Au; Haiyi Yu; Lin Xu; Jia Jia; Robert M. Porsch; Lijie Sun; Weixian Xu; Huiping Zheng; Lai-Yung Wong; Yiming Mu; Jingtao Dou; Carol H. Y. Fong; Shuyu Wang; Xueyu Hong; Liguang Dong; Yanhua Liao; Jiansong Wang; Levina S. M. Lam; Xi Su; Hua Yan; Min-Lee Yang; Jin Chen; Chung-Wah Siu; Gaoqiang Xie; Yu-Cho Woo; Yangfeng Wu; Kathryn C. B. Tan; Kristian Hveem; Bernard M. Y. Cheung; Sebastian Zöllner; Aimin Xu; Y Eugene Chen; Chao Qiang Jiang; Youyi Zhang; Tai-Hing Lam; Santhi K. Ganesh; Yong Huo; Pak C. Sham; Karen S. L. Lam; Cristen J. Willer; Hung-Fat Tse; Wei Gao
• Keywords: Exome; Sequence (biology); Coding region

Abstract 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 analysis on 65,671 single nucleotide polymorphisms reveals 19 associated with at 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 two novel loci— PNPLA3 p.Ile148Met PKD1L3 p.Thr429Ser — also influence levels of triglycerides low-density lipoprotein cholesterol, respectively. Another gene, TEAD2 , is found be high-density cholesterol through gene-based analysis. Most these newly identified show suggestive <0.05) CAD. These findings demonstrate that samples non-European ancestry can population-specific possible causal variants, shedding light biology