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

Open access
DIAGRAM Consortium, Cho, Yoon Shin, MuTHER Consortium, Chen, Chien-Hsiun, Hu, Cheng, Long, Jirong, Hee Ong, Rick Twee, 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, Åsa 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·2012·Nature Genetics

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.

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Authors
DIAGRAM Consortium, Cho, Y. S., MuTHER Consortium, 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., Gao, Y., Hu, F. B., Kim, H.-L., Kim, S., Kim, Y. J., Lee, J. J.-M., Lee, N. R., Li, Y., Liu, J. J., Lu, W., Nakamura, J., Nakashima, E., Ng, D. P.-K., Tay, W. T., Tsai, F.-J., Wong, T. Y., Yokota, M., Zheng, W., Zhang, R., Wang, C., So, W. Y., Ohnaka, K., Ikegami, H., Hara, K., Cho, Y. M., Cho, N. H., Chang, T.-J., Bao, Y., Hedman, Å. K., Morris, A. P., McCarthy, M. I., Takayanagi, R., Park, K. S., Jia, W., Chuang, L.-M., Chan, J. C. N., Maeda, S., Kadowaki, T., Lee, J.-Y., Wu, J.-Y., Teo, Y. Y., Tai, E. S., Shu, X. O., Mohlke, K. L., Kato, N., Han, B.-G., & Seielstad, M.
Venue
Nature Genetics
Published
2011-12-11
Volume
44
Issue
1
Pages
67-72
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2169189827
Cited by
611
References
7
FWCI
4.94
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. https://app.cochat.ai/papers/10.1038/ng.1019
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DIAGRAM Consortium, Cho, Y. S., MuTHER Consortium, 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., . . . Seielstad, M. (2012). Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. Nature Genetics. https://doi.org/10.1038/ng.1019

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