A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B

Toshimasa Yamauchi, Kazuo Hara, Shiro Maeda, Kazuki Yasuda, Atsushi Takahashi, Momoko Horikoshi, Masahiro Nakamura, Hayato Fujita, Niels Grarup, Stephane Cauchi, Daniel P.K. Ng, Ronald C.W. Ma, Tatsuhiko Tsunoda, Michiaki Kubo, Hirotaka Watada, Hiroshi Maegawa, Miki Okada-Iwabu, Masato Iwabu, Nobuhiro Shojima, Hyoung Doo ShinGitte Andersen, Daniel R. Witte, Torben Jørgensen, Torsten Lauritzen, Annelli Sandbæk, Torben Hansen, Toshihiko Ohshige, Shintaro Omori, Ikuo Saito, Kohei Kaku, Hiroshi Hirose, Wing Yee So, Delphine Beury, Juliana C.N. Chan, Kyong Soo Park, E. Shyong Tai, Chikako Ito, Yasushi Tanaka, Atsunori Kashiwagi, Ryuzo Kawamori, Masato Kasuga, Philippe Froguel, Oluf Pedersen, Naoyuki Kamatani, Yusuke Nakamura, Takashi Kadowaki

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Abstract

We conducted a genome-wide association study of type 2 diabetes (T2D) using 459,359 SNPs in a Japanese population with a three-stage study design (stage 1, 4,470 cases and 3,071 controls; stage 2, 2,886 cases and 3,087 controls; stage 3, 3,622 cases and 2,356 controls). We identified new associations in UBE2E2 on chromosome 3 and in C2CD4A-C2CD4B on chromosome 15 at genome-wide significant levels (rs7612463 in UBE2E2, combined P = 2.27 × 10 -9; rs7172432 in C2CD4A-C2CD4B, combined P = 3.66 × 10 -9). The association of these two loci with T2D was replicated in other east Asian populations. In the European populations, the C2CD4A-C2CD4B locus was significantly associated with T2D, and a combined analysis of all populations gave P = 8.78 × 10 -14, whereas the UBE2E2 locus did not show association to T2D. In conclusion, we identified two new loci at UBE2E2 and C2CD4A-C2CD4B associated with susceptibility to T2D.

Original languageEnglish
Pages (from-to)864-868
Number of pages5
JournalNature Genetics
Volume42
Issue number10
DOIs
Publication statusPublished - 01-10-2010

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All Science Journal Classification (ASJC) codes

  • Genetics

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Yamauchi, T., Hara, K., Maeda, S., Yasuda, K., Takahashi, A., Horikoshi, M., Nakamura, M., Fujita, H., Grarup, N., Cauchi, S., Ng, D. P. K., Ma, R. C. W., Tsunoda, T., Kubo, M., Watada, H., Maegawa, H., Okada-Iwabu, M., Iwabu, M., Shojima, N., ... Kadowaki, T. (2010). A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B. Nature Genetics, 42(10), 864-868. https://doi.org/10.1038/ng.660