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

Yoon Shin Cho, Chien Hsiun Chen, Cheng Hu, Jirong Long, Rick Twee Hee Ong, Xueling Sim, Fumihiko Takeuchi, Ying Wu, Min Jin Go, Toshimasa Yamauchi, Yi Cheng Chang, Soo Heon Kwak, Ronald C.W. Ma, Ken Yamamoto, Linda S. Adair, Tin Aung, Qiuyin Cai, Li Ching Chang, Yuan Tsong Chen, Yutang GaoFrank B. Hu, Hyung Lae Kim, Sangsoo Kim, Young Jin Kim, Jeannette Jen Mai Lee, Nanette R. Lee, Yun Li, Jian Jun Liu, Wei Lu, Jiro Nakamura, Eitaro Nakashima, Daniel Peng Keat Ng, Wan Ting Tay, Fuu Jen Tsai, Tien Yin Wong, Mitsuhiro Yokota, Wei Zheng, Rong Zhang, Congrong Wang, Wing Yee So, Keizo Ohnaka, Hiroshi Ikegami, Kazuo Hara, Young Min Cho, Nam H. Cho, Tien Jyun Chang, Yuqian Bao, Åsa K. Hedman, Andrew P. Morris, Mark I. McCarthy, Ryoichi Takayanagi, Kyong Soo Park, Weiping Jia, Lee Ming Chuang, Juliana C.N. Chan, Shiro Maeda, Takashi Kadowaki, Jong Young Lee, Jer Yuarn Wu, Yik Ying Teo, E. Shyong Tai, Xiao Ou Shu, Karen L. Mohlke, Norihiro Kato, Bok Ghee Han, Mark Seielstad

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Abstract

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, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A 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.

Original languageEnglish
Pages (from-to)67-72
Number of pages6
JournalNature genetics
Volume44
Issue number1
DOIs
Publication statusPublished - Jan 1 2012

All Science Journal Classification (ASJC) codes

  • Genetics

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    Cho, Y. S., Chen, C. H., Hu, C., Long, J., Hee Ong, R. T., Sim, X., Takeuchi, F., Wu, Y., Go, M. J., Yamauchi, T., Chang, Y. C., Kwak, S. H., Ma, R. C. W., Yamamoto, K., Adair, L. S., Aung, T., Cai, Q., Chang, L. C., Chen, Y. T., ... Seielstad, M. (2012). Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. Nature genetics, 44(1), 67-72. https://doi.org/10.1038/ng.1019