Association study of 71 European Crohn's disease susceptibility loci in a Japanese population

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)526-533
Number of pages8
JournalInflammatory Bowel Diseases
Volume19
Issue number3
DOIs
Publication statusPublished - 01-03-2013

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Disease Susceptibility
Crohn Disease
Single Nucleotide Polymorphism
Population
Phenotype
Genotype
Genome-Wide Association Study
Meta-Analysis
Immune System

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Cite this

Hirano, Atsushi ; Yamazaki, Keiko ; Umeno, Junji ; Ashikawa, Kyota ; Aoki, Masayuki ; Matsumoto, Takayuki ; Nakamura, Shotaro ; Ninomiya, Toshiharu ; Matsui, Toshiyuki ; Hirai, Fumihito ; Kawaguchi, Takaaki ; Takazoe, Masakazu ; Tanaka, Hiroki ; Motoya, Satoshi ; Kiyohara, Yutaka ; Kitazono, Takanari ; Nakamura, Yusuke ; Kamatani, Naoyuki ; Kubo, Michiaki. / Association study of 71 European Crohn's disease susceptibility loci in a Japanese population. In: Inflammatory Bowel Diseases. 2013 ; Vol. 19, No. 3. pp. 526-533.
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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.",
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Hirano, A, Yamazaki, K, Umeno, J, Ashikawa, K, Aoki, M, Matsumoto, T, Nakamura, S, Ninomiya, T, Matsui, T, Hirai, F, Kawaguchi, T, Takazoe, M, Tanaka, H, Motoya, S, Kiyohara, Y, Kitazono, T, Nakamura, Y, Kamatani, N & Kubo, M 2013, 'Association study of 71 European Crohn's disease susceptibility loci in a Japanese population', Inflammatory Bowel Diseases, vol. 19, no. 3, pp. 526-533. https://doi.org/10.1097/MIB.0b013e31828075e7

Association study of 71 European Crohn's disease susceptibility loci in a Japanese population. / Hirano, Atsushi; Yamazaki, Keiko; Umeno, Junji; Ashikawa, Kyota; Aoki, Masayuki; Matsumoto, Takayuki; Nakamura, Shotaro; Ninomiya, Toshiharu; Matsui, Toshiyuki; Hirai, Fumihito; Kawaguchi, Takaaki; Takazoe, Masakazu; Tanaka, Hiroki; Motoya, Satoshi; Kiyohara, Yutaka; Kitazono, Takanari; Nakamura, Yusuke; Kamatani, Naoyuki; Kubo, Michiaki.

In: Inflammatory Bowel Diseases, Vol. 19, No. 3, 01.03.2013, p. 526-533.

Research output: Contribution to journalArticle

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 - 2013/3/1

Y1 - 2013/3/1

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.

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