TY - JOUR
T1 - Association study of 71 European Crohn's disease susceptibility loci in a Japanese population
AU - Hirano, Atsushi
AU - Yamazaki, Keiko
AU - Umeno, Junji
AU - Ashikawa, Kyota
AU - Aoki, Masayuki
AU - Matsumoto, Takayuki
AU - Nakamura, Shotaro
AU - Ninomiya, Toshiharu
AU - Matsui, Toshiyuki
AU - Hirai, Fumihito
AU - Kawaguchi, Takaaki
AU - Takazoe, Masakazu
AU - Tanaka, Hiroki
AU - Motoya, Satoshi
AU - Kiyohara, Yutaka
AU - Kitazono, Takanari
AU - Nakamura, Yusuke
AU - Kamatani, Naoyuki
AU - Kubo, Michiaki
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
KW - Crohn's disease
KW - Innate immune system
KW - Japanese
KW - TNFSF15
UR - http://www.scopus.com/inward/record.url?scp=84876373775&partnerID=8YFLogxK
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U2 - 10.1097/MIB.0b013e31828075e7
DO - 10.1097/MIB.0b013e31828075e7
M3 - Article
C2 - 23388546
AN - SCOPUS:84876373775
SN - 1078-0998
VL - 19
SP - 526
EP - 533
JO - Inflammatory bowel diseases
JF - Inflammatory bowel diseases
IS - 3
ER -