Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

被引：164

作者：

Wen, Wanqing ^{[1
]}

Zheng, Wei ^{[1
]}

Okada, Yukinori ^{[2
,6
]}

Takeuchi, Fumihiko ^{[7
]}

Tabara, Yasuharu ^{[8
]}

Hwang, Joo-Yeon ^{[9
]}

Dorajoo, Rajkumar ^{[10
,11
]}

Li, Huaixing ^{[12
,13
]}

Tsai, Fuu-Jen ^{[14
,15
,17
]}

Yang, Xiaobo ^{[18
,19
]}

He, Jiang ^{[20
]}

Wu, Ying ^{[21
]}

He, Meian ^{[22
,23
]}

Zhang, Yi ^{[24
,25
]}

Liang, Jun ^{[26
]}

Guo, Xiuqing ^{[27
,28
]}

Sheu, Wayne Huey-Herng ^{[29
,30
,31
]}

Delahanty, Ryan ^{[1
]}

Guo, Xingyi ^{[1
]}

Kubo, Michiaki ^{[3
]}

Yamamoto, Ken ^{[32
]}

Ohkubo, Takayoshi ^{[33
,34
]}

Go, Min Jin ^{[9
]}

Liu, Jian Jun ^{[10
]}

Gan, Wei ^{[12
,13
]}

Chen, Ching-Chu ^{[14
,16
]}

Gao, Yong ^{[19
,35
]}

Li, Shengxu ^{[20
]}

Lee, Nanette R. ^{[36
]}

Wu, Chen ^{[37
,38
]}

Zhou, Xueya ^{[39
]}

Song, Huaidong ^{[40
]}

Yao, Jie ^{[27
,28
]}

Lee, I-Te ^{[29
,41
]}

Long, Jirong ^{[1
]}

Tsunoda, Tatsuhiko ^{[4
]}

Akiyama, Koichi ^{[7
]}

Takashima, Naoyuki ^{[34
]}

Cho, Yoon Shin ^{[9
,42
]}

Ong, Rick T. H. ^{[10
,43
,44
]}

Lu, Ling ^{[12
,13
]}

Chen, Chien-Hsiun ^{[14
,45
]}

Tan, Aihua ^{[19
]}

Rice, Treva K. ^{[46
]}

Adair, Linda S. ^{[47
]}

Gui, Lixuan ^{[22
,23
]}

Allison, Matthew ^{[48
]}

Lee, Wen-Jane ^{[50
,51
]}

Cai, Qiuyin ^{[1
]}

Isomura, Minoru ^{[52
]}

机构：

[1] Vanderbilt Univ, Div Epidemiol, Vanderbilt Epidemiol Ctr, Dept Med,Vanderbilt Ingram Canc Ctr,Sch Med, Nashville, TN 37203 USA

[2] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan

[3] RIKEN Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[4] RIKEN Ctr Integrat Med Sci, Lab Med Sci Math, Yokohama, Kanagawa, Japan

[5] RIKEN Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan

[6] Tokyo Med & Dent Univ, Dept Human Genet & Dis Divers, Grad Sch Med & Dent Sci, Tokyo, Japan

[7] Natl Ctr Global Hlth & Med, Dept Gene Diagnost & Therapeut, Res Inst, Tokyo, Japan

[8] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan

[9] Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea

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

[11] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Genom Common Dis, Sch Publ Hlth, London, England

[12] Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

[13] Chinese Acad Sci, Grad Sch, Shanghai 200031, Peoples R China

[14] China Med Univ Hosp, Sch Chinese Med, Taichung, Taiwan

[15] China Med Univ Hosp, Dept Med Genet, Taichung, Taiwan

[16] China Med Univ Hosp, Dept Med, Div Endocrinol & Metab, Taichung, Taiwan

[17] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung, Taiwan

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

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

[20] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA

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

[22] Huazhong Univ Sci & Technol, Dept Occupat & Environm Hlth, Wuhan 430030, Hubei, Peoples R China

[23] Huazhong Univ Sci & Technol, Minist Educ, Key Lab Environm & Hlth, Sch Publ Hlth,Tongji Med Coll, Wuhan 430030, Hubei, Peoples R China

[24] Shanghai Jiao Tong Univ, Sch Med, Shanghai Ruijin Hosp, State Key Lab Med Genet, Shanghai 200030, Peoples R China

[25] Shanghai Res Inst Hypertens, Shanghai, Peoples R China

[26] Southeast Univ, Dept Endocrinol, Xuzhou Cent Hosp, Xuzhou Clin Sch,Xuzhou Med Coll,Affiliated Hosp, Xuzhou 221009, Jiangsu, Peoples R China

[27] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA

[28] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA

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

[30] Natl Def Med Ctr, Coll Med, Taipei, Taiwan

[31] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan

[32] Kyushu Univ, Med Inst Bioregulat, Dept Mol Genet, Fukuoka 812, Japan

[33] Tohoku Univ, Grad Sch Pharmaceut Sci, Dept Planning Drug Dev & Clin Evaluat, Sendai, Miyagi 980, Japan

[34] Shiga Univ Med Sci, Dept Hlth Sci, Otsu, Shiga 52021, Japan

[35] Guangxi Med Univ, Coll Gen Practice, Nanning, Guangxi, Peoples R China

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

[37] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100730, Peoples R China

[38] Peking Union Med Coll, Beijing 100021, Peoples R China

[39] Tsinghua Natl Lab Informat Sci & Technol, Bioinformat Div, Beijing, Peoples R China

[40] Shanghai Jiao Tong Univ, State Key Lab Med Genom, Ruijin Hosp, Mol Med Ctr,Shanghai Inst Endocrinol,Sch Med, Shanghai 200030, Peoples R China

[41] Chung Shan Med Univ, Dept Med, Taichung, Taiwan

[42] Hallym Univ, Dept Biomed Sci, Gangwon Do, South Korea

[43] Natl Univ Singapore, NUS Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore

[44] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore

[45] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[46] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA

[47] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA

[48] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA

[49] Univ Calif San Diego, NShiley Eye Ctr, Dept Ophthalmol, La Jolla, CA 92093 USA

[50] Taichung Vet Gen Hosp, Dept Med Res, Taichung, Taiwan

来源：

HUMAN MOLECULAR GENETICS | 2014年 / 23卷 / 20期

基金：

美国国家卫生研究院; 中国国家自然科学基金; 日本学术振兴会; 英国医学研究理事会; 日本科学技术振兴机构; 新加坡国家研究基金会;

关键词：

CORONARY-ARTERY-DISEASE; COMMON VARIANTS; BLOOD-PRESSURE; JAPANESE POPULATION; GENETIC-VARIANTS; SUSCEPTIBILITY LOCI; DRINKING BEHAVIOR; ADULT OBESITY; QT INTERVAL; RISK LOCI;

D O I：

10.1093/hmg/ddu248

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and similar to 2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 x 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 x 10(-11); rs12229654, P = 4.56 x 10(-9)), ITIH4 (rs2535633, P = 1.77 x 10(-18)) and NT5C2 (rs11191580, P = 3.83 x 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 x 10(-8)) and an additional 14 at P < 1.0 x 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

引用

页码：5492 / 5504

页数：13

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