Abstract:
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.
journal_name
J Gastroenteroljournal_title
Journal of gastroenterologyauthors
Fuyuno Y,Yamazaki K,Takahashi A,Esaki M,Kawaguchi T,Takazoe M,Matsumoto T,Matsui T,Tanaka H,Motoya S,Suzuki Y,Kiyohara Y,Kitazono T,Kubo Mdoi
10.1007/s00535-015-1135-3subject
Has Abstractpub_date
2016-07-01 00:00:00pages
672-81issue
7eissn
0944-1174issn
1435-5922pii
10.1007/s00535-015-1135-3journal_volume
51pub_type
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