Journal Article

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

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

2015

Overview

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. An important risk factor for coronary artery disease is the level of blood lipids. Here the authors conduct an exome-wide association study in Chinese cohorts and identify three novel loci associated with lipid levels as well as three Asian-specific variants in known loci.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/208/205/2138 / 692/699/75/2099 / 692/699/75/593/15 / 692/700/478/174 / Asian Continental Ancestry Group - genetics / Cardiology / Cardiovascular disease / Cholesterol / Cholesterol, HDL - metabolism / Cholesterol, LDL - metabolism / Coronary vessels / Exome - genetics / Gene loci / Genetic Variation / Genotype / High density lipoprotein / Hospitals / Humanities and Social Sciences / Humans / Laboratories / Lipid Metabolism - genetics / Lipids / Lipoproteins / Medicine / Metabolic disorders / multidisciplinary / Public health / Risk factors / Science / Science (multidisciplinary) / Triglycerides - metabolism / Vein & artery diseases