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 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

192 Citations (Scopus)

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 language	English
Journal	Nature Genetics
Volume	42
Issue number	10
Pages (from-to)	864-8
Number of pages	5
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.660
Publication status	Published - 1 Oct 2010

Keywords

Asian Continental Ancestry Group
Case-Control Studies
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 3
Diabetes Mellitus, Type 2
Genetic Predisposition to Disease
Genome, Human
Genome-Wide Association Study
Genotype
Humans
Polymorphism, Single Nucleotide
Transcription Factors
Ubiquitin-Conjugating Enzymes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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), 864-8. https://doi.org/10.1038/ng.660

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, W-Y, 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. 864-8. https://doi.org/10.1038/ng.660

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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 × 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.",

keywords = "Asian Continental Ancestry Group, Case-Control Studies, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 3, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Transcription Factors, Ubiquitin-Conjugating Enzymes",

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 Wing-Yee So 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",

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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

PY - 2010/10/1

Y1 - 2010/10/1

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.

KW - Asian Continental Ancestry Group

KW - Case-Control Studies

KW - Chromosomes, Human, Pair 15

KW - Chromosomes, Human, Pair 3

KW - Diabetes Mellitus, Type 2

KW - Genetic Predisposition to Disease

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Polymorphism, Single Nucleotide

KW - Transcription Factors

KW - Ubiquitin-Conjugating Enzymes

U2 - 10.1038/ng.660

DO - 10.1038/ng.660

M3 - Journal article

C2 - 20818381

SN - 1061-4036

VL - 42

SP - 864

EP - 868

JO - Nature: New biology

JF - Nature: New biology

IS - 10

ER -

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

Abstract

Keywords

UN SDGs

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