Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants that contribute to lipid levels and coronary artery disease

被引：125

作者：

Lu, Xiangfeng ^{[1
,2
,3
,4
]}

Peloso, Gina M. ^{[5
,6
]}

Liu, Dajiang J. ^{[7
]}

Wu, Ying ^{[8
]}

Zhang, He ^{[3
,4
]}

Zhou, Wei ^{[9
]}

Li, Jun ^{[10
]}

Tang, Clara Sze-man ^{[11
,12
]}

Dorajoo, Rajkumar ^{[13
]}

Li, Huaixing ^{[14
,15
]}

Long, Jirong ^{[16
]}

Guo, Xiuqing ^{[17
]}

Xu, Ming ^{[18
]}

Spracklen, Cassandra N.

Chen, Yang ^{[19
,20
]}

Liu, Xuezhen

Zhang, Yan ^{[21
]}

Khor, Chiea Chuen ^{[13
,22
,23
]}

Liu, Jianjun ^{[13
]}

Sun, Liang ^{[14
,15
]}

Wang, Laiyuan ^{[1
,2
]}

Gao, Yu-Tang ^{[24
]}

Hu, Yao ^{[14
,15
]}

Yu, Kuai ^{[10
]}

Wang, Yiqin ^{[14
,15
]}

Cheung, Chloe Yu Yan ^{[25
]}

Wang, Feijie ^{[14
,15
]}

Huang, Jianfeng ^{[1
,2
,26
]}

Fan, Qiao ^{[23
,27
]}

Cai, Qiuyin ^{[16
]}

Chen, Shufeng ^{[1
,2
]}

Shi, Jinxiu ^{[28
]}

Yang, Xueli ^{[1
,2
]}

Zhao, Wanting ^{[23
]}

Sheu, Wayne H-H ^{[29
]}

Cherny, Stacey Shawn ^{[30
,31
,32
]}

He, Meian ^{[10
]}

Feranil, Alan B. ^{[33
,34
]}

Adair, Linda S. ^{[35
]}

Gordon-Larsen, Penny ^{[35
,36
]}

Du, Shufa ^{[35
,36
]}

Varma, Rohit ^{[37
]}

Chen, Yii-Der Ida ^{[17
]}

Shu, Xiao-Ou ^{[16
]}

Lam, Karen Siu Ling ^{[38
,39
]}

Wong, Tien Yin ^{[22
,27
,40
,41
]}

Ganesh, Santhi K. ^{[3
,4
]}

Mo, Zengnan ^{[19
,20
]}

Hveem, Kristian ^{[42
,43
,44
]}

Fritsche, Lars G. ^{[42
,43
,45
]}

机构：

[1] Chinese Acad Med Sci, Dept Epidemiol, State Key Lab Cardiovasc Dis, Fuwai Hosp,Natl Ctr Cardiovasc Dis, Beijing, Peoples R China

[2] Peking Union Med Coll, Beijing, Peoples R China

[3] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA

[5] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[6] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[7] Penn State Univ, Inst Personalized Med, Dept Publ Hlth Sci, University Pk, PA 16802 USA

[8] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[9] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

[10] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, MOE Key Lab Environm & Hlth, Wuhan, Hubei, Peoples R China

[11] Univ Hong Kong, Li KaShing Fac Med, Dept Surg, Hong Kong, Hong Kong, Peoples R China

[12] Univ Hong Kong, Karolinska Inst Collaborat Regenerat Med, Li Dak Sum Res Ctr, Hong Kong, Hong Kong, Peoples R China

[13] Genome Inst Singapore, Agcy Sci Technol & Res, Singapore, Singapore

[14] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab, Inst Nutrit Sci, Shanghai, Peoples R China

[15] Univ Chinese Acad Sci, Shanghai, Peoples R China

[16] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Dept Med,Div Epidemiol, Nashville, TN 37212 USA

[17] Harbor UCLA Med Ctr, LABioMed, Inst Translat Genom & Populat Sci, Los Angeles, CA USA

[18] Peking Univ Third Hosp, Dept Cardiol, Inst Vasc Med, Key Lab Mol Cardiovasc Sci,Minist Educ, Beijing, Peoples R China

[19] Guangxi Med Univ, Ctr Genom & Personalized Med, Med Sci Res Ctr, Nanning, Peoples R China

[20] Guangxi Med Univ, Dept Occupat Hlth & Environm Hlth, Sch Publ Hlth, Nanning, Peoples R China

[21] Peking Univ, Hosp 1, Dept Cardiol, Beijing, Peoples R China

[22] Natl Univ Singapore, Natl Univ Hlth Syst, Dept Biochem, Yong Loo Lin Sch Med, Singapore, Singapore

[23] Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore

[24] Shanghai Jiao Tong Univ, Sch Med, Dept Epidemiol, Shanghai Canc Inst,Renji Hosp, Shanghai, Peoples R China

[25] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China

[26] Shenzhen Univ, Affiliated Hosp 3, Community Hlth Ctr, Shenzhen, Peoples R China

[27] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore

[28] Chinese Natl Human Genome Ctr Shanghai, Dept Genet, Shanghai MOST Key Lab Hlth & Dis Gen, Shanghai, Peoples R China

[29] Taichung Vet Gen Hosp, Div Endocrine Metab, Dept Internal Med, Taichung, Taiwan

[30] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China

[31] Univ Hong Kong, Li KaShing Fac Med, Ctr Genom Sci, Hong Kong, Hong Kong, Peoples R China

[32] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China

[33] Univ San Carlos, USC Off Populat Studies Fdn, Cebu, Philippines

[34] Univ San Carlos, Dept Anthropol Sociol & Hist, Cebu, Philippines

[35] Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA

[36] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA

[37] Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Eye Inst, Los Angeles, CA 90033 USA

[38] Univ Hong Kong, Res Ctr Heart Brain Hormone & Healthy Aging, Li KaShing Fac Med, Hong Kong, Hong Kong, Peoples R China

[39] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong, Hong Kong, Peoples R China

[40] Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore

[41] Natl Univ Singapore, Dept Ophthalmol, Singapore, Singapore

[42] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway

[43] Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, Trondheim, Norway

[44] Nord Trondelag Hosp Trust, Levanger Hosp, Dept Med, Levanger, Norway

[45] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA

[46] Univ Hong Kong, Hong Kong Guangdong Joint Lab Stem Cell & Regener, Hong Kong, Hong Kong, Peoples R China

[47] Ophthalmol & Visual Sci Acad Clin Program, Duke NUS Med Sch, Singapore, Singapore

[48] Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore

[49] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA

来源：

NATURE GENETICS | 2017年 / 49卷 / 12期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; LOW-FREQUENCY; BLOOD-LIPIDS; MYOCARDIAL-INFARCTION; SEQUENCE VARIANTS; RARE VARIANTS; RISK; CHOLESTEROL; GENE; TRIGLYCERIDES;

D O I：

10.1038/ng.3978

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.

引用

页码：1722 / +

页数：14

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