Genetic characteristics of inflammatory bowel disease in a Japanese population.
BACKGROUND
Crohn's disease (CD) and ulcerative colitis (UC) are two major forms of inflammatory bowel disease (IBD). Meta-analyses of genome-wide association studies (GWAS) have identified 163 susceptibility loci for IBD among European populations; however, there is limited information for IBD susceptibility in a Japanese population.


METHODS
We performed a GWAS using imputed genotypes of 743 IBD patients (372 with CD and 371 with UC) and 3321 controls. Using 100 tag single-nucleotide polymorphisms (SNPs) (P < 5 × 10(-5)), a replication study was conducted with an independent set of 1310 IBD patients (949 with CD and 361 with UC) and 4163 controls. In addition, 163 SNPs identified by a European IBD GWAS were genotyped, and genetic backgrounds were compared between the Japanese and European populations.


RESULTS
In the IBD GWAS, two East Asia-specific IBD susceptibility loci were identified in the Japanese population: ATG16L2-FCHSD2 and SLC25A15-ELF1-WBP4. Among 163 reported SNPs in European IBD patients, significant associations were confirmed in 18 (8 CD-specific, 4 UC-specific, and 6 IBD-shared). In Japanese CD patients, genes in the Th17-IL23 pathway showed stronger genetic effects, whereas the association of genes in the autophagy pathway was limited. The association of genes in the epithelial barrier and the Th17-IL23R pathways were similar in the Japanese and European UC populations.


CONCLUSIONS
We confirmed two IBD susceptibility loci as common for CD and UC, and East Asian-specific. The genetic architecture in UC appeared to be similar between Europeans and East Asians, but may have some differences in CD.
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Japan.|Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yuta
Y
Fuyuno
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Japan.
Keiko
K
Yamazaki
Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
Atsushi
A
Takahashi
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Motohiro
M
Esaki
Division of Gastroenterology, Department of Medicine, Tokyo Yamate Medical Center, Tokyo, Japan.
Takaaki
T
Kawaguchi
Division of Gastroenterology, Department of Medicine, Tokyo Yamate Medical Center, Tokyo, Japan.
Masakazu
M
Takazoe
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takayuki
T
Matsumoto
Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
Toshiyuki
T
Matsui
Department of Gastroenterology, Sapporo-Kosei General Hospital, Sapporo, Japan.
Hiroki
H
Tanaka
Department of Gastroenterology, Sapporo-Kosei General Hospital, Sapporo, Japan.
Satoshi
S
Motoya
Department of Internal Medicine, Faculty of Medicine, Toho University, Chiba, Japan.
Yasuo
Y
Suzuki
Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yutaka
Y
Kiyohara
Division of Gastroenterology, Department of Medicine, Tokyo Yamate Medical Center, Tokyo, Japan.
Takanari
T
Kitazono
Center for Integrative Medical Sciences, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan. michiaki.kubo@riken.jp.
Michiaki
M
Kubo
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000208:ethnology / Q000235:genetics*; D003424:Crohn Disease / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics*; D055815:Young Adult
Crohn’s disease; Ethnic difference; Genome-wide association study; Inflammatory bowel disease; Ulcerative colitis