Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

被引：477

作者：

Cho, Yoon Shin ^{[1
]}

Chen, Chien-Hsiun ^{[2
,3
]}

Hu, Cheng ^{[4
]}

Long, Jirong ^{[5
]}

Ong, Rick Twee Hee ^{[6
]}

Sim, Xueling ^{[7
]}

Takeuchi, Fumihiko

Wu, Ying ^{[9
]}

Go, Min Jin ^{[1
]}

Yamauchi, Toshimasa ^{[10
]}

Chang, Yi-Cheng ^{[11
]}

Kwak, Soo Heon ^{[12
]}

Ma, Ronald C. W. ^{[13
]}

Yamamoto, Ken ^{[14
]}

Adair, Linda S. ^{[15
]}

Aung, Tin ^{[16
,17
]}

Cai, Qiuyin

Chang, Li-Ching ^{[2
]}

Chen, Yuan-Tsong ^{[2
]}

Gao, Yutang ^{[18
]}

Hu, Frank B. ^{[19
]}

Kim, Hyung-Lae ^{[1
,20
]}

Kim, Sangsoo ^{[21
]}

Kim, Young Jin ^{[1
]}

Lee, Jeannette Jen-Mai ^{[22
]}

Lee, Nanette R. ^{[23
]}

Li, Yun ^{[9
,24
]}

Liu, Jian Jun ^{[25
]}

Lu, Wei ^{[26
]}

Nakamura, Jiro ^{[27
]}

Nakashima, Eitaro ^{[27
,28
]}

Ng, Daniel Peng-Keat ^{[22
]}

Tay, Wan Ting ^{[16
]}

Tsai, Fuu-Jen ^{[3
]}

Wong, Tien Yin ^{[16
,17
,28
,29
]}

Yokota, Mitsuhiro ^{[30
]}

Zheng, Wei

Zhang, Rong

Wang, Congrong ^{[4
]}

So, Wing Yee ^{[13
]}

Ohnaka, Keizo ^{[31
]}

Ikegami, Hiroshi ^{[32
]}

Hara, Kazuo ^{[10
]}

Cho, Young Min ^{[12
]}

Cho, Nam H. ^{[33
]}

Chang, Tien-Jyun ^{[11
]}

Bao, Yuqian ^{[4
]}

Hedman, Asa K. ^{[34
]}

Morris, Andrew P. ^{[34
]}

McCarthy, Mark I. ^{[34
,35
]}

机构：

[1] Natl Inst Hlth, Ctr Genome Sci, Gangoe Myeon, Yeonje Ri, South Korea

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

[3] China Med Univ, Sch Chinese Med, Taichung, Taiwan

[4] Shanghai Jiao Tong Univ, Dept Endocrinol & Metab, Affiliated Peoples Hosp 6, Shanghai Diabet Inst,Shanghai Key Lab Diabet Mell, Shanghai 200030, Peoples R China

[5] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA

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

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

[8] Natl Ctr Global Hlth & Med, Res Inst, Shinjuku Ku, Tokyo, Japan

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

[10] Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo, Japan

[11] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan

[12] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea

[13] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China

[14] Kyushu Univ, Med Inst Bioregulat, Res Ctr Genet Informat, Div Genome Anal,Higashi Ku, Fukuoka 812, Japan

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

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

[17] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore

[18] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China

[19] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA

[20] Ewha Womans Univ, Sch Med, Dept Biochem, Seoul, South Korea

[21] Soongsil Univ, Sch Syst Biomed Sci, Seoul, South Korea

[22] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore

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

[24] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA

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

[26] Shanghai Inst Prevent Med, Shanghai, Peoples R China

[27] Nagoya Univ, Grad Sch Med, Dept Internal Med, Div Endocrinol & Diabet, Nagoya, Aichi 4648601, Japan

[28] Chubu Rosai Hosp, Dept Endocrinol & Diabet, Nagoya, Aichi, Japan

[29] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia

[30] Aichi Gakuin Univ, Sch Dent, Dept Genome Sci, Nagoya, Aichi 464, Japan

[31] Kyushu Univ, Dept Geriatr Med, Grad Sch Med Sci, Higashi Ku, Fukuoka 812, Japan

[32] Kinki Univ, Sch Med, Dept Endocrinol Metab & Diabet, Osaka 589, Japan

[33] Ajou Univ, Sch Med, Dept Prevent Med, Suwon 441749, South Korea

[34] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[35] Univ Oxford, Oxford Ctr Diabet Edocrinol & Metab, Churchill Hosp, Oxford, England

[36] Kyushu Univ, Dept Internal Med & Bioregulatory Sci, Grad Sch Med Sci, Higashi Ku, Fukuoka 812, Japan

[37] Seoul Natl Univ, World Class Univ Program, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul, South Korea

[38] Seoul Natl Univ, Coll Med, Seoul, South Korea

[39] Natl Taiwan Univ, Sch Med, Grad Inst Clin Med, Taipei 10764, Taiwan

[40] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore

[41] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore

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

[43] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

[44] Blood Syst Res Inst, San Francisco, CA USA

来源：

NATURE GENETICS | 2012年 / 44卷 / 01期

基金：

中国国家自然科学基金; 英国医学研究理事会; 新加坡国家研究基金会; 美国国家卫生研究院;

关键词：

SUSCEPTIBILITY LOCI; JAPANESE POPULATION; GENETIC-LOCI; VARIANTS; RISK; CHILDHOOD; MELLITUS; COMPLEX; KCNQ1;

D O I：

10.1038/ng.1019

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression(1,2), is known for its association with fasting glucose levels(3,4). The evidence of an association with T2D for PEPD(5) and HNF4A(6,7) has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.

引用

页码：67 / U97

页数：7

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