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

被引:76
|
作者
Tang, Clara S. [1 ]
Zhang, He [2 ]
Cheung, Chloe Y. Y. [3 ]
Xu, Ming [4 ]
Ho, Jenny C. Y. [3 ]
Zhou, Wei [2 ,5 ]
Cherny, Stacey S. [1 ,6 ,7 ]
Zhang, Yan [8 ]
Holmen, Oddgeir [9 ,10 ]
Au, Ka-Wing [3 ]
Yu, Haiyi [4 ]
Xu, Lin
Jia, Jia [8 ]
Porsch, Robert M. [1 ]
Sun, Lijie [4 ]
Xu, Weixian [4 ]
Zheng, Huiping [4 ]
Wong, Lai-Yung [3 ]
Mu, Yiming
Dou, Jingtao
Fong, Carol H. Y. [3 ]
Wang, Shuyu [13 ]
Hong, Xueyu [3 ]
Dong, Liguang [12 ,14 ]
Liao, Yanhua [12 ,14 ]
Wang, Jiansong [12 ,14 ]
Lam, Levina S. M. [6 ]
Su, Xi [15 ]
Yan, Hua [15 ]
Yang, Min-Lee [2 ]
Chen, Jin [2 ]
Siu, Chung-Wah [3 ,16 ]
Xie, Gaoqiang [17 ]
Woo, Yu-Cho [3 ]
Wu, Yangfeng [18 ]
Tan, Kathryn C. B. [3 ,16 ]
Hveem, Kristian [9 ]
Cheung, Bernard M. Y. [3 ,11 ,16 ,19 ]
Zoellner, Sebastian [20 ]
Xu, Aimin [3 ,11 ,16 ,19 ,21 ]
Chen, Eugene [2 ]
Jiang, Chao Qiang [22 ]
Zhang, Youyi [23 ]
Lam, Tai-Hing
Ganesh, Santhi K. [2 ,24 ]
Huo, Yong [8 ]
Sham, Pak C. [1 ,6 ,7 ]
Lam, Karen S. L. [3 ,11 ,16 ,19 ]
Willer, Cristen J. [2 ,5 ,24 ]
Tse, Hung-Fat [3 ,16 ,25 ]
机构
[1] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China
[2] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA
[3] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China
[4] Peking Univ, Hosp 3, Dept Cardiol, Key Lab Mol Cardiovasc Sci,Inst Vasc Med,Minist E, Beijing 100871, Peoples R China
[5] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA
[6] Univ Hong Kong, Ctr Genom Sci, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China
[7] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China
[8] Peking Univ, Hosp 1, Dept Cardiol, Beijing 100871, Peoples R China
[9] Norwegian Univ Sci & Technol, HUNT Res Ctr, Dept Publ Hlth & Gen Practice, N-7600 Levanger, Norway
[10] Univ Trondheim Hosp, St Olav Hosp, N-7030 Trondheim, Norway
[11] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China
[12] Chinese Peoples Liberat Army Gen Hosp, Dept Endocrinol, Beijing 100853, Peoples R China
[13] Beijing Hypertens League Inst, Beijing 100039, Peoples R China
[14] Peking Univ, Shougang Hosp, Beijing 100871, Peoples R China
[15] Wuhan Asia Heart Hosp, Dept Cardiol, Wuhan, Peoples R China
[16] Univ Hong Kong, Li Ka Shing Fac Med, Res Ctr Heart Brain Hormone & Healthy Aging, Hong Kong, Hong Kong, Peoples R China
[17] Peking Univ, Clin Res Inst, Beijing 100871, Peoples R China
[18] Peking Univ, Sch Publ Hlth, Clin Res Inst, Dept Epidemiol & Biostat, Beijing 100871, Peoples R China
[19] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong, Hong Kong, Peoples R China
[20] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA
[21] Univ Hong Kong, Dept Pharmacol & Pharm, Hong Kong, Hong Kong, Peoples R China
[22] Guangzhou 12 Hosp, Guangzhou 510620, Guangdong, Peoples R China
[23] Peking Univ, Hosp 3, Beijing Key Lab Cardiovasc Receptors Res, Inst Vasc Med, Beijing 100191, Peoples R China
[24] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
[25] Univ Hong Kong, Hong Kong Guangdong Joint Lab Stem Cell & Regener, Hong Kong, Hong Kong, Peoples R China
[26] Peking Univ, Hosp 3, Key Lab Cardiovasc Mol Biol & Regulatory Pept, Minist Hlth,Dept Cardiol, Beijing 100191, Peoples R China
关键词
OF-FUNCTION MUTATIONS; FATTY LIVER-DISEASE; CONFERS SUSCEPTIBILITY; GLYCEMIC TRAITS; LOW-FREQUENCY; PNPLA3; RARE; CHOLESTEROL; PLASMA; APOC3;
D O I
10.1038/ncomms10206
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 Human-Exome 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 x 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.
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页数:9
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