A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.
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Authors
Li, Huaixing
Gan, Wei
Lu, Ling
Dong, Xiao
Han, Xueyao
Hu, Cheng
Yang, Zhen
Sun, Liang
Bao, Wei
Li, Pengtao
He, Meian
Sun, Liangdan
Wang, Yiqin
Zhu, Jingwen
Ning, Qianqian
Tang, Yong
Zhang, Rong
Wen, Jie
Wang, Di
Zhu, Xilin
Guo, Kunquan
Zuo, Xianbo
Guo, Xiaohui
Yang, Handong
Zhou, Xianghai
DIAGRAM Consortium,
AGEN-T2D Consortium,
Zhang, Xuejun
Qi, Lu
Hu, Frank B
Wu, Tangchun
Liu, Ying
Liu, Liegang
Yang, Ze
Hu, Renming
Jia, Weiping
Ji, Linong
Li, Yixue
Lin, Xu
Publication Date
2013-01Journal Title
Diabetes
ISSN
0012-1797
Volume
62
Issue
1
Pages
291-298
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Li, H., Gan, W., Lu, L., Dong, X., Han, X., Hu, C., Yang, Z., et al. (2013). A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.. Diabetes, 62 (1), 291-298. https://doi.org/10.2337/db12-0454
Abstract
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 × 10(-9)) and RASGRP1 (rs7403531: P = 3.9 × 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 β-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.
Keywords
DIAGRAM Consortium, AGEN-T2D Consortium, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Blood Glucose, Guanine Nucleotide Exchange Factors, DNA-Binding Proteins, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, China, Adiposity, G-Protein-Coupled Receptor Kinase 5, Genome-Wide Association Study, Genetic Loci
Sponsorship
MEDICAL RESEARCH COUNCIL (MC_U106188470)
NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC) (HTA/08/116/300)
MRC (MC_UU_12015/4)
Identifiers
External DOI: https://doi.org/10.2337/db12-0454
This record's URL: https://www.repository.cam.ac.uk/handle/1810/273429
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: http://creativecommons.org/licenses/by-nc-nd/4.0/
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