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

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

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.

引用

页数：9

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