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

被引：215

作者：

Yamauchi, Toshimasa ^{[1
,2
]}

Hara, Kazuo ^{[1
]}

Maeda, Shiro ^{[3
]}

Yasuda, Kazuki ^{[4
]}

Takahashi, Atsushi ^{[5
]}

Horikoshi, Momoko ^{[1
]}

Nakamura, Masahiro ^{[1
]}

Fujita, Hayato ^{[1
]}

Grarup, Niels ^{[6
]}

Cauchi, Stephane ^{[7
,8
]}

Ng, Daniel P. K. ^{[9
]}

Ma, Ronald C. W. ^{[10
]}

Tsunoda, Tatsuhiko ^{[11
]}

Kubo, Michiaki ^{[12
]}

Watada, Hirotaka ^{[13
]}

Maegawa, Hiroshi ^{[14
]}

Okada-Iwabu, Miki ^{[1
,2
]}

Iwabu, Masato ^{[1
,2
]}

Shojima, Nobuhiro ^{[1
]}

Shin, Hyoung Doo ^{[15
]}

Andersen, Gitte ^{[6
]}

Witte, Daniel R. ^{[16
,17
]}

Jorgensen, Torben ^{[18
,19
]}

Lauritzen, Torsten ^{[20
]}

Sandbaek, Annelli ^{[20
]}

Hansen, Torben ^{[6
,16
,21
]}

Ohshige, Toshihiko ^{[22
]}

Omori, Shintaro ^{[22
]}

Saito, Ikuo ^{[23
]}

Kaku, Kohei ^{[24
]}

Hirose, Hiroshi ^{[23
]}

So, Wing-Yee ^{[10
]}

Beury, Delphine ^{[7
,8
]}

Chan, Juliana C. N. ^{[10
]}

Park, Kyong Soo ^{[25
]}

Tai, E. Shyong ^{[26
]}

Ito, Chikako ^{[27
]}

Tanaka, Yasushi ^{[22
]}

Kashiwagi, Atsunori ^{[14
]}

Kawamori, Ryuzo

Kasuga, Masato ^{[28
]}

Froguel, Philippe ^{[7
,29
]}

Pedersen, Oluf ^{[6
,17
,19
]}

Kamatani, Naoyuki

Nakamura, Yusuke ^{[30
]}

Kadowaki, Takashi ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo, Japan

[2] Univ Tokyo, Dept Integrated Mol Sci Metab Dis, Century Med & Res Ctr 22, Tokyo, Japan

[3] Ctr Gen Med, RIKEN, Lab Endocrinol & Metab, Yokohama, Kanagawa, Japan

[4] Res Inst, Diabet Res Ctr, Dept Metab Disorder, Natl Ctr Global Hlth & Med, Tokyo, Japan

[5] Ctr Genom Med, RIKEN, Lab Stat Anal, Yokohama, Kanagawa, Japan

[6] Hagedorn Res Inst, Gentofte, Denmark

[7] Inst Biol, Ctr Natl Rech Sci, Unit Mixte Rech 8090, Lille, France

[8] Univ Lille 2, Inst Pasteur, Lille, France

[9] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore

[10] Chinese Univ Hong Kong, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China

[11] Ctr Genom Med, RIKEN, Lab Med Informat, Yokohama, Kanagawa, Japan

[12] Ctr Genom Med, RIKEN, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[13] Juntendo Univ, Grad Sch Med, Dept Med Metab & Endocrinol, Tokyo, Japan

[14] Shiga Univ Med Sci, Dept Med, Otsu, Shiga 52021, Japan

[15] Sogang Univ, Dept Life Sci, Lab Genom Div, Seoul, South Korea

[16] Steno Diabet Ctr, DK-2820 Gentofte, Denmark

[17] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark

[18] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark

[19] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark

[20] Univ Aarhus, Dept Gen Practice, Aarhus, Denmark

[21] Univ So Denmark, Fac Hlth Sci, Odense, Denmark

[22] St Marianna Univ, Sch Med, Dept Med, Kawasaki, Kanagawa, Japan

[23] Keio Univ, Ctr Hlth, Tokyo, Japan

[24] Kawasaki Med Sch, Dept Internal Med, Div Endocrinol & Metab, Kurashiki, Okayama, Japan

[25] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea

[26] Natl Univ Singapore, Dept Med, Yong Loo Lin Sch Med, Singapore 117548, Singapore

[27] Med Court Life Care Clin, Hiroshima, Japan

[28] Res Inst, Natl Ctr Global Hlth & Med, Diabet Res Ctr, Tokyo, Japan

[29] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Centre & Dept Genom Med, London, England

[30] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan

来源：

NATURE GENETICS | 2010年 / 42卷 / 10期

基金：

英国医学研究理事会;

关键词：

UBIQUITIN-PROTEASOME SYSTEM; FASTING PLASMA-GLUCOSE; INSULIN-RESISTANCE; GENETIC-VARIATION; RISK LOCI; VARIANT; REPLICATION; STRATIFICATION; HOMEOSTASIS; MTNR1B;

D O I：

10.1038/ng.660

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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 x 10(-9); rs7172432 in C2CD4A-C2CD4B, combined P = 3.66 x 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 x 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.

引用

页码：864 / +

页数：6

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