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

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 DouCarol 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number10206
JournalNature Communications
StatePublished - 22 Dec 2015
Externally publishedYes


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