A Genome-Wide Association Study Identifies 2 Susceptibility Loci for Crohn's Disease in a Japanese Population

被引：113

作者：

Yamazaki, Keiko ^{[1
]}

Umeno, Junji ^{[1
,4
]}

Takahashi, Atsushi ^{[2
]}

Hirano, Atsushi ^{[1
,4
]}

Johnson, Todd Andrew ^{[3
]}

Kumasaka, Natsuhiko ^{[2
]}

Morizono, Takashi ^{[3
]}

Hosono, Naoya ^{[1
]}

Kawaguchi, Takaaki ^{[5
]}

Takazoe, Masakazu ^{[5
]}

Yamada, Tetsuhiro ^{[6
]}

Suzuki, Yasuo ^{[6
]}

Tanaka, Hiroki ^{[7
]}

Motoya, Satoshi ^{[7
,8
]}

Hosokawa, Masayo ^{[8
]}

Arimura, Yoshiaki ^{[8
]}

Shinomura, Yasuhisa ^{[8
]}

Matsui, Toshiyuki ^{[9
]}

Matsumoto, Takayuki ^{[4
]}

Iida, Mitsuo ^{[4
]}

Tsunoda, Tatsuhiko ^{[3
]}

Nakamura, Yusuke ^{[10
]}

Kamatani, Naoyuki ^{[2
]}

Kubo, Michiaki ^{[1
]}

机构：

[1] RIKEN, Inst Phys & Chem Res, Ctr Genom Med, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[2] RIKEN, Inst Phys & Chem Res, Ctr Genom Med, Lab Stat Anal, Yokohama, Kanagawa, Japan

[3] RIKEN, Inst Phys & Chem Res, Ctr Genom Med, Lab Med Informat, Yokohama, Kanagawa, Japan

[4] Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka 812, Japan

[5] Social Insurance Chuo Gen Hosp, Div Gastroenterol, Dept Med, Tokyo, Japan

[6] Toho Univ, Fac Med, Dept Internal Med, Chiba 2748510, Japan

[7] Sapporo Kosei Hosp, Dept Gastroenterol, Sapporo, Hokkaido, Japan

[8] Sapporo Med Univ, Sch Med, Dept Internal Med 1, Sapporo, Hokkaido, Japan

[9] Fukuoka Univ, Chikushi Hosp, Dept Gastroenterol, Fukuoka 81401, Japan

[10] Univ Tokyo, Inst Med Sci, Mol Med Lab, Tokyo, Japan

来源：

GASTROENTEROLOGY | 2013年 / 144卷 / 04期

关键词：

Inflammatory Bowel Disease; GWAS; Polymorphism; CD; INFLAMMATORY-BOWEL-DISEASE; GENETIC-VARIANTS; GENOTYPES; METAANALYSIS; NUCLEOTIDE; EXPRESSION; AUTOPHAGY; SEQUENCE; ATG16L1; NUMBER;

D O I：

10.1053/j.gastro.2012.12.021

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

BACKGROUND & AIMS: Crohn's disease is an inflammatory bowel disease induced by multiple genetic and environmental factors. Genome-wide association studies have identified genetic factors that affect the risk for Crohn's disease in European populations, but information from other ethnic groups is scarce. We therefore investigated genetic factors associated with Crohn's disease in the Japanese population. METHODS: We performed a genome-wide association study with 372 individuals with Crohn's disease (cases) and 3389 controls, all from the Japanese population. To confirm identified associations, we performed a replication study with an independent panel of 1151 Crohn's disease cases and 15,800 controls. We also performed an association analysis using genome-wide genotype imputation in the discovery cohort. RESULTS: We confirmed associations of Crohn's disease with variants in MHC (rs7765379, P = 2.11 X 10(-59)), TNFSF15 (rs6478106, P = 3.87 X 10(-45)), and STAT3 (rs9891119, P = 2.24 X 10(-14)). We identified 2 new susceptibility loci: on chromosome 4p14 (rs1487630, P = 2.40 X 10(-11); odds ratio, 1.33), and in the SLC25A15 ELF1-WBP4 region on 13q14 (rs7329174 in ELF1, P = 5.12 X 10(-9); odds ratio, 1.27). CONCLUSIONS: In a genome-wide association study, we identified 2 new susceptibility loci for Crohn's disease in a Japanese population. These findings could increase our understanding of the pathogenesis of Crohn's disease.

引用

页码：781 / 788

页数：8

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