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 Shin; Gitte 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

doi:10.1038/ng.660

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 Shin

Gitte 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

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

237 被引用数 (Scopus)

抄録

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.

本文言語	英語
ページ（範囲）	864-868
ページ数	5
ジャーナル	Nature Genetics
巻	42
号	10
DOI	https://doi.org/10.1038/ng.660
出版ステータス	出版済み - 10-2010
外部発表	はい

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All Science Journal Classification (ASJC) codes

遺伝学

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10.1038/ng.660

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引用スタイル

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

@article{127b5206bdbb450aabf320912b3e6b01,

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

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 {\texttimes} 10 -9; rs7172432 in C2CD4A-C2CD4B, combined P = 3.66 {\texttimes} 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 {\texttimes} 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.",

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

note = "Funding Information: The Korean panel was supported by a grant from the Korea Health 21 Research and Development Project, Ministry of Health, Welfare, and Family Affairs, Republic of Korea (00-PJ3-PG6-GN07-001). The Danish study was funded by grants from the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LuCAMP), European Union (EUGENE2) grant LSHM-CT-2004-512013, EXGENESIS (Health benefits of exercise: identification of genes and signaling pathways involved in effects of exercise on insulin resistance, obesity and the metabolic syndrome) grant LSHM-CT-2004-005272 and the Danish Diabetes Association and the Danish Agency for Science, Technology and Innovation, grant no. 271-06-0539. The Inter99 was initiated by T. J{\o}rgensen (primary investigator), K. Borch-Johnsen (co-primary investigator), H. Ibsen and T.F. Thomsen. The steering committee comprises T. J{\o}rgensen, K. Borch-Johnsen and C. Pisinger. The ADDITION (The Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care) study Denmark was initiated by K. Borch-Johnsen (primary investigator), T. Lauritzen (primary investigator) and A. Sandb{\ae}k. Funding Information: genotyping. We also thank all the participants and the staff of the BioBank Japan project. This work was partly supported by a grant from the Leading Project of Ministry of Education, Culture, Sports, Science and Technology Japan. Funding Information: Funding for the Singapore portion of the study was supported by the National Medical Research Council (NMRC/1115/2007). We thank the staff of the National Healthcare Group Polyclinics and the National University of Singapore for their contributions towards the establishment of the Singapore Diabetes Cohort Study.",

year = "2010",

month = oct,

doi = "10.1038/ng.660",

language = "English",

volume = "42",

pages = "864--868",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "10",

}

Yamauchi, T, Hara, K, Maeda, S, Yasuda, K, Takahashi, A, Horikoshi, M, Nakamura, M, Fujita, H, Grarup, N, Cauchi, S, Ng, DPK, Ma, RCW, Tsunoda, T, Kubo, M, Watada, H, Maegawa, H, Okada-Iwabu, M, Iwabu, M, Shojima, N, Shin, HD, Andersen, G, Witte, DR, Jørgensen, T, Lauritzen, T, Sandbæk, A, Hansen, T, Ohshige, T, Omori, S, Saito, I, Kaku, K, Hirose, H, So, WY, Beury, D, Chan, JCN, Park, KS, Tai, ES, Ito, C, Tanaka, Y, Kashiwagi, A, Kawamori, R, Kasuga, M, Froguel, P, Pedersen, O, Kamatani, N, Nakamura, Y & 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, vol. 42, no. 10, pp. 864-868. https://doi.org/10.1038/ng.660

TY - JOUR

T1 - A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B

AU - Yamauchi, Toshimasa

AU - Hara, Kazuo

AU - Maeda, Shiro

AU - Yasuda, Kazuki

AU - Takahashi, Atsushi

AU - Horikoshi, Momoko

AU - Nakamura, Masahiro

AU - Fujita, Hayato

AU - Grarup, Niels

AU - Cauchi, Stephane

AU - Ng, Daniel P.K.

AU - Ma, Ronald C.W.

AU - Tsunoda, Tatsuhiko

AU - Kubo, Michiaki

AU - Watada, Hirotaka

AU - Maegawa, Hiroshi

AU - Okada-Iwabu, Miki

AU - Iwabu, Masato

AU - Shojima, Nobuhiro

AU - Shin, Hyoung Doo

AU - Andersen, Gitte

AU - Witte, Daniel R.

AU - Jørgensen, Torben

AU - Lauritzen, Torsten

AU - Sandbæk, Annelli

AU - Hansen, Torben

AU - Ohshige, Toshihiko

AU - Omori, Shintaro

AU - Saito, Ikuo

AU - Kaku, Kohei

AU - Hirose, Hiroshi

AU - So, Wing Yee

AU - Beury, Delphine

AU - Chan, Juliana C.N.

AU - Park, Kyong Soo

AU - Tai, E. Shyong

AU - Ito, Chikako

AU - Tanaka, Yasushi

AU - Kashiwagi, Atsunori

AU - Kawamori, Ryuzo

AU - Kasuga, Masato

AU - Froguel, Philippe

AU - Pedersen, Oluf

AU - Kamatani, Naoyuki

AU - Nakamura, Yusuke

AU - Kadowaki, Takashi

N1 - Funding Information: The Korean panel was supported by a grant from the Korea Health 21 Research and Development Project, Ministry of Health, Welfare, and Family Affairs, Republic of Korea (00-PJ3-PG6-GN07-001). The Danish study was funded by grants from the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LuCAMP), European Union (EUGENE2) grant LSHM-CT-2004-512013, EXGENESIS (Health benefits of exercise: identification of genes and signaling pathways involved in effects of exercise on insulin resistance, obesity and the metabolic syndrome) grant LSHM-CT-2004-005272 and the Danish Diabetes Association and the Danish Agency for Science, Technology and Innovation, grant no. 271-06-0539. The Inter99 was initiated by T. Jørgensen (primary investigator), K. Borch-Johnsen (co-primary investigator), H. Ibsen and T.F. Thomsen. The steering committee comprises T. Jørgensen, K. Borch-Johnsen and C. Pisinger. The ADDITION (The Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care) study Denmark was initiated by K. Borch-Johnsen (primary investigator), T. Lauritzen (primary investigator) and A. Sandbæk. Funding Information: genotyping. We also thank all the participants and the staff of the BioBank Japan project. This work was partly supported by a grant from the Leading Project of Ministry of Education, Culture, Sports, Science and Technology Japan. Funding Information: Funding for the Singapore portion of the study was supported by the National Medical Research Council (NMRC/1115/2007). We thank the staff of the National Healthcare Group Polyclinics and the National University of Singapore for their contributions towards the establishment of the Singapore Diabetes Cohort Study.

PY - 2010/10

Y1 - 2010/10

N2 - 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.

AB - 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.

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U2 - 10.1038/ng.660

DO - 10.1038/ng.660

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AN - SCOPUS:77957553197

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VL - 42

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JO - Nature Genetics

JF - Nature Genetics

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