A Genome-Wide Association Study Identifies GRK5 and RASGRP1 as Type 2 Diabetes Loci in Chinese Hans

被引：174

作者：

Li, Huaixing ^{[1
,2
]}

Gan, Wei ^{[1
,2
]}

Lu, Ling ^{[1
,2
]}

Dong, Xiao ^{[2
,3
]}

Han, Xueyao ^{[4
]}

Hu, Cheng ^{[5
]}

Yang, Zhen ^{[6
]}

Sun, Liang ^{[7
,8
]}

Bao, Wei ^{[9
,10
]}

Li, Pengtao ^{[11
]}

He, Meian ^{[10
,12
]}

Sun, Liangdan ^{[13
,14
,15
]}

Wang, Yiqin ^{[1
,2
]}

Zhu, Jingwen ^{[1
,2
]}

Ning, Qianqian ^{[2
,3
]}

Tang, Yong ^{[4
]}

Zhang, Rong ^{[5
]}

Wen, Jie ^{[6
]}

Wang, Di ^{[9
,10
]}

Zhu, Xilin ^{[11
]}

Guo, Kunquan ^{[10
,12
]}

Zuo, Xianbo ^{[13
,14
,15
]}

Guo, Xiaohui ^{[18
]}

Yang, Handong ^{[16
,17
]}

Zhou, Xianghai ^{[4
]}

Zhang, Xuejun ^{[13
,14
,15
]}

Qi, Lu ^{[19
]}

Loos, Ruth J. F. ^{[20
,21
]}

Hu, Frank B. ^{[19
]}

Wu, Tangchun ^{[10
,12
]}

Liu, Ying ^{[11
]}

Liu, Liegang ^{[9
,10
]}

Yang, Ze ^{[7
,8
]}

Hu, Renming ^{[6
]}

Jia, Weiping ^{[5
]}

Ji, Linong ^{[4
]}

Li, Yixue ^{[2
,3
,22
,23
]}

Lin, Xu ^{[1
,2
]}

机构：

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

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

[3] Chinese Acad Sci, Key Lab Syst Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China

[4] Peking Univ, Dept Endocrinol & Metab, Peoples Hosp, Beijing 100871, Peoples R China

[5] Shanghai Jiao Tong Univ, Dept Endocrinol & Metab, Shanghai Diabet Inst,Peoples Hosp 6, Shanghai Key Lab Diabet Mellitus,Shanghai Clin Ct, Shanghai 200030, Peoples R China

[6] Fudan Univ, Inst Endocrinol & Diabetol, Huashan Hosp, Shanghai Med Coll, Shanghai 200433, Peoples R China

[7] Minist Hlth, Beijing Inst Geriatr, Beijing, Peoples R China

[8] Beijing Hosp, Key Lab Geriatr, Beijing, Peoples R China

[9] Huazhong Univ Sci & Technol, Dept Food Hyg & Nutr, Sch Publ Hlth, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China

[10] Huazhong Univ Sci & Technol, Minist Educ Key Lab Environm & Hlth, Sch Publ Hlth, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China

[11] Chinese Acad Med Sci, Inst Basic Med Sci, State Key Lab Med Mol Biol, Sch Basic Med,Peking Union Med Coll, Beijing 100730, Peoples R China

[12] Huazhong Univ Sci & Technol, Inst Occupat Med, Sch Publ Hlth, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China

[13] Anhui Med Univ, Inst Dermatol, Hosp 1, Hefei, Anhui, Peoples R China

[14] Anhui Med Univ, Dept Dermatol, Hosp 1, Hefei, Anhui, Peoples R China

[15] Minist Natl Sci & Technol, State Key Lab Incubat Base Dermatol, Hefei, Anhui, Peoples R China

[16] Hubei Univ Med, Shiyan, Hubei, Peoples R China

[17] Dongfeng Motor Corp, Dongfeng Cent Hosp, Shiyan, Hubei, Peoples R China

[18] Peking Univ, Hosp 1, Beijing 100871, Peoples R China

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

[20] Mt Sinai Sch Med, Dept Prevent Med, Charles R Bronfman Inst Personalized Med, New York, NY USA

[21] Mt Sinai Sch Med, Dept Prevent Med, Child Hlth & Dev Inst, New York, NY USA

[22] Shanghai Ctr Bioinformat Technol, Shanghai, Peoples R China

[23] Shanghai Jiao Tong Univ, Coll Life Sci & Biotechnol, Shanghai 200030, Peoples R China

来源：

DIABETES | 2013年 / 62卷 / 01期

基金：

国家高技术研究发展计划(863计划); 中国国家自然科学基金;

关键词：

SUSCEPTIBILITY LOCI; RECEPTOR; CELL; PHOSPHORYLATION; GLUCOSE; INTERNALIZATION; REPLICATION; HOMEOSTASIS; ACTIVATION; VARIANTS;

D O I：

10.2337/db12-0454

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 x 10(-9)) and RASGRP1 (rs7403531: P = 3.9 x 10-9), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA(1c), and lower homeostasis model assessment of beta-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility. Diabetes 62:291-298, 2013

引用

页码：291 / 298

页数：8

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