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Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4
作者: Li, H.14,15; Hon, K. L.6; Ma, R. C. W.1,2,3; Hu, C.4,5; Tam, C. H.1; Zhang, R.4; Kwan, P.1; Leung, T. F.6; Thomas, G. N.7; Go, M. J.8; Hara, K.9,10; Sim, X.11,12,13; Ho, J. S. K.1; Wang, C.4; Lu, L.14,15; Wang, Y.1,14,15; Li, J. W.16; Wang, Y.1; Lam, V. K. L.1; Wang, J.4; Yu, W.4; Kim, Y. J.8; Ng, D. P.17; Fujita, H.9; Panoutsopoulou, K.18; Day-Williams, A. G.18; Lee, H. M.1; Ng, A. C. W.1; Fang, Y-J.19; Kong, A. P. S.1; Jiang, F.4; Ma, X.4; Hou, X.4; Tang, S.4; Lu, J.4; Yamauchi, T.9; Tsui, S. K. W.20; Woo, J.1; Leung, P. C.21; Zhang, X.5; Tang, N. L. S.22; Sy, H. Y.6; Liu, J.23; Wong, T. Y.24,25,26; Lee, J. Y.8; Maeda, S.27; Xu, G.1; Cherny, S. S.28,29; Chan, T. F.16; Ng, M. C. Y.30; Xiang, K.4; Morris, A. P.31; Keildson, S.31; Hu, R.32; Ji, L.33; Lin, X.14,15; Cho, Y. S.34; Kadowaki, T.9; Tai, E. S.35,36; Zeggini, E.18; McCarthy, M. I.31,37; Baum, L.38; Tomlinson, B.1; So, W. Y.1; Bao, Y.4; Chan, J. C. N.1,2,3; Jia, W.4; DIAGRAM Consortium1; MuTHER Consortium1
关键词: Chinese ; Diabetes ; East Asians ; Genetics ; Genome-wide association study
刊名: DIABETOLOGIA
发表日期: 2013-06-01
DOI: 10.1007/s00125-013-2874-4
卷: 56, 期:6, 页:1291-1305
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Endocrinology & Metabolism
研究领域[WOS]: Endocrinology & Metabolism
关键词[WOS]: HUMAN PANCREATIC-ISLETS ; GENE ; METAANALYSIS ; MUTATIONS ; VARIANTS ; LINKAGE ; POLYMORPHISMS ; EXPRESSION ; MELLITUS ; JAPANESE
英文摘要:

Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.

We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.

We identified CDKN2A/B and four novel type 2 diabetes association signals with p < 1 x 10(-5) from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (p (meta) = 2.6 x 10(-8); OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (p (meta) = 2.3 x 10(-10)) and a population of European descent (p = 8.6 x 10(-3)). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians.

Our study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.

语种: 英语
所属项目编号: NIH-RFA DK-085545-01 ; 469908 ; 470909 ; 3110034 ; 3110060 ; HKU762308M ; CUHK4466/06M ; 461708 ; HKU7672/06M ; CUHK 1/04C ; CUHK4724/07M ; ITS/088/08 ; ITS/487/09FP
项目资助者: National Institutes of Health (from the National Institute of Diabetes and Digestive and Kidney Diseases) ; Chinese University Focused Investment Fund ; Chinese University Direct Grant ; Research Fund of the Department of Medicine and Therapeutics and the Diabetes ; Research Grants Council General Research Fund ; CUHK Research Committee Group ; Research Grants Council of the Hong Kong Special Administrative Region, China ; Sir Michael and Lady Kadoorie Funded Research Into Cancer Genetics ; CUHK ; RGC ; Research Grants Council Earmarked Research Fund ; Hong Kong Foundation for Research and Development in Diabetes ; Chinese University of Hong Kong ; Hong Kong Governments Research Grant Committee Central Allocation Scheme ; Research Grants Council ; Innovation and Technology Fund
WOS记录号: WOS:000318787600012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50233
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA
2.Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China
3.Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China
4.Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China
5.Chinese Univ Hong Kong, Li Ka Shing Inst Life Sci, Hong Kong, Hong Kong, Peoples R China
6.Shanghai Jiao Tong Univ, Shanghai Key Clin Ctr Metab Dis, Shanghai Key Lab Diabet Mellitus,Shanghai Clin Ct, Shanghai Diabet Inst,Affiliated Peoples Hosp 6,De, Shanghai 200233, Peoples R China
7.Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai 200233, Peoples R China
8.Chinese Univ Hong Kong, Dept Paediat, Hong Kong, Hong Kong, Peoples R China
9.Univ Birmingham, Dept Publ Hlth Epidemiol & Biostat, Birmingham, W Midlands, England
10.Natl Inst Hlth, Ctr Genome Sci, Cheongwon Gun, Chungcheongbuk, South Korea
11.Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo, Japan
12.Tokyo Univ Hosp, Dept Integrated Mol Sci Metab Dis, Tokyo 113, Japan
13.Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Ctr Mol Epidemiol, Singapore 117548, Singapore
14.Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA
15.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China
16.Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China
17.Chinese Univ Hong Kong, Sch Life Sci, Hong Kong, Hong Kong, Peoples R China
18.Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore
19.Wellcome Trust Sanger Inst, Cambridge, England
20.Sun Yat Sen Univ, Ctr Canc, Dept Colorectal Surg, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China
21.Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China
22.Chinese Univ Hong Kong, Dept Orthopaed, Hong Kong, Hong Kong, Peoples R China
23.Chinese Univ Hong Kong, Dept Chem Pathol, Hong Kong, Hong Kong, Peoples R China
24.Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore
25.Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore
26.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore
27.Univ Melbourne, Ctr Eye Res Australia, East Melbourne, Vic, Australia
28.RIKEN Ctr Genom Med, Lab Endocrinol & Metab, Yokohama, Kanagawa, Japan
29.Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China
30.Wake Forest Sch Med, Ctr Diabet Res, Ctr Genom & Personalized Med Res, Winston Salem, NC USA
31.Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
32.Fudan Univ, Shanghai Med Coll, Huashan Hosp, Inst Endocrinol & Diabetol, Shanghai 200433, Peoples R China
33.Peking Univ, Peoples Hosp, Dept Endocrinol & Metab, Beijing 100871, Peoples R China
34.Hallym Univ, Dept Biomed Sci, Chunchon, Gangwon Do, South Korea
35.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore
36.Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore
37.Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England
38.Chinese Univ Hong Kong, Sch Pharm, Hong Kong, Hong Kong, Peoples R China

Recommended Citation:
Li, H.,Hon, K. L.,Ma, R. C. W.,et al. Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4[J]. DIABETOLOGIA,2013,56(6):1291-1305.
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