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Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e31828075e7
Original Basic Science Articles

Association Study of 71 European Crohn's Disease Susceptibility Loci in a Japanese Population

Hirano, Atsushi MD*,†; Yamazaki, Keiko DVM, PhD*; Umeno, Junji MD, PhD*,†; Ashikawa, Kyota MS*; Aoki, Masayuki MD, PhD*; Matsumoto, Takayuki MD, PhD; Nakamura, Shotaro MD, PhD; Ninomiya, Toshiharu MD, PhD; Matsui, Toshiyuki MD, PhD§; Hirai, Fumihito MD, PhD§; Kawaguchi, Takaaki MD; Takazoe, Masakazu MD; Tanaka, Hiroki MD, PhD; Motoya, Satoshi MD, PhD; Kiyohara, Yutaka MD, PhD; Kitazono, Takanari MD, PhD; Nakamura, Yusuke MD, PhD**; Kamatani, Naoyuki MD, PhD*; Kubo, Michiaki MD, PhD*

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Abstract

Background: A large-scale meta-analysis of a series of European genome-wide association studies revealed 71 susceptibility loci for Crohn's disease (CD). However, it is not clear whether these susceptibility loci are also shared with Japanese populations.

Methods: We genotyped 71 single-nucleotide polymorphisms (SNPs) comprising 1311 CD cases and 6585 controls of Japanese descent, and their associations with CD were evaluated using the Cochran–Armitage trend test. In addition, genotype–phenotype analyses were conducted on the SNPs showing associations with Japanese CD based on the Montreal classification.

Results: Twenty-seven SNPs showed at least nominal association (P < 0.05) and 11 of them remained significant even after Bonferroni correction (P < 0.0007). Despite high statistical power, we could not find any association in 17 loci. Moreover, SNPs in 9 loci were rare or absent in the Japanese population. Genetic variations involved in the innate immune system (NOD2, ATG16L1, and IRGM) showed no association with CD susceptibility in the Japanese population. Genotype–phenotype analyses showed that rs3810936, a marker of TNFSF15, correlated with severe CD phenotypes.

Conclusions: Our study suggests that there is a differential genetic background of CD susceptibility between Japanese and European populations.

© Crohn's & Colitis Foundation of America, Inc.

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