A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.
A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.
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全基因组关联研究确定 GRK5 和 RASGRP1 为中国汉族 2 型糖尿病基因座
作者：
Li H;Gan W;Lu L;Dong X;Han X;Hu C;Yang Z;Sun L;Bao W;Li P;He M;Sun L;Wang Y;Zhu J;Ning Q;Tang Y;Zhang R;Wen J;Wang D;Zhu X;Guo K;Zuo X;Guo X;Yang H;Zhou X;DIAGRAM Consortium;AGEN-T2D Consortium;Zhang X;Qi L;Loos RJ;Hu FB;Wu T;Liu Y;Liu L;Yang Z;Hu R;Jia W;Ji L;Li Y;Lin X
在过去的几年中，2型糖尿病（T2D）风险位点的鉴定取得了实质性进展，但我们对不同种族人群中T2D的遗传基础的了解仍然有限。我们在中国汉族中进行了一项全基因组关联研究和一项复制研究，共包括8,569例T2D病例和8,923例对照，从中选择10个单核苷酸多态性，在3,410例T2D病例和3,412例对照样本中进行了进一步的随访，并在6,952例T2D病例和11,865例对照中进行了计算机复制。除了确认7个已建立的T2D基因座（CDKAL1、CDKN2A/B、KCNQ1、CDC123、GLIS3、HNF1B和DUSP9）具有全基因组意义外，我们还发现了两个新的T2D基因座，包括g蛋白偶联受体激酶5 (GRK5) （rs10886471: P = 7.1 × 10−9）和RASGRP1 (rs7403531: P = 3.9 × 10−9)，其中GRK5的关联信号似乎是东亚人特异性的。在非糖尿病个体中，T2D风险增加等位基因RASGRP1-rs7403531也与较高的HbA1c和较低的β细胞功能稳态模型评估相关（P分别为0.03和0.0209），而T2D风险增加等位基因GRK5-rs10886471也与较高的空腹胰岛素相关（P = 0.0169），但与空腹血糖无关。我们的研究结果不仅为T2D的病理生理学提供了新的见解，而且可能揭示了T2D易感性的种族差异。
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 HbA1c 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.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
G蛋白偶联受体激酶5的HIP磷酸化调节趋化因子受体CXCR4的内在化。
影响因子：
2.9
作者：
Barker, Breann L.;Benovic, Jeffrey L.
通讯作者：
Benovic, Jeffrey L.
全基因组关联研究的荟萃分析确定了东亚人 2 型糖尿病的 8 个新位点
影响因子：
30.8
作者：
Cho, Yoon Shin;Chen, Chien-Hsiun;Hu, Cheng;Long, Jirong;Ong, Rick Twee Hee;Sim, Xueling;Takeuchi, Fumihiko;Wu, Ying;Go, Min Jin;Yamauchi, Toshimasa;Chang, Yi-Cheng;Kwak, Soo Heon;Ma, Ronald C. W.;Yamamoto, Ken;Adair, Linda S.;Aung, Tin;Cai, Qiuyin;Chang, Li-Ching;Chen, Yuan-Tsong;Gao, Yutang;Hu, Frank B.;Kim, Hyung-Lae;Kim, Sangsoo;Kim, Young Jin;Lee, Jeannette Jen-Mai;Lee, Nanette R.;Li, Yun;Liu, Jian Jun;Lu, Wei;Nakamura, Jiro;Nakashima, Eitaro;Ng, Daniel Peng-Keat;Tay, Wan Ting;Tsai, Fuu-Jen;Wong, Tien Yin;Yokota, Mitsuhiro;Zheng, Wei;Zhang, Rong;Wang, Congrong;So, Wing Yee;Ohnaka, Keizo;Ikegami, Hiroshi;Hara, Kazuo;Cho, Young Min;Cho, Nam H.;Chang, Tien-Jyun;Bao, Yuqian;Hedman, Asa K.;Morris, Andrew P.;McCarthy, Mark I.;Takayanagi, Ryoichi;Park, Kyong Soo;Jia, Weiping;Chuang, Lee-Ming;Chan, Juliana C. N.;Maeda, Shiro;Kadowaki, Takashi;Lee, Jong-Young;Wu, Jer-Yuarn;Teo, Yik Ying;Tai, E. Shyong;Shu, Xiao Ou;Mohlke, Karen L.;Kato, Norihiro;Han, Bok-Ghee;Seielstad, Mark
通讯作者：
Seielstad, Mark
影响因子：
32.4
作者：
Priatel, JJ;Teh, SJ;Teh, HS
通讯作者：
Teh, HS
影响因子：
4.4
作者：
Coughlin, JJ;Stang, SL;Stone, JC
通讯作者：
Stone, JC