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.
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.
Authors: Chengrui Huang; Talin Haritunians; David T Okou; Dermot P B McGovern; Steven R Brant; Subra Kugathasan; David J Cutler; Michael E Zwick; Kent D Taylor; Lisa W Datta; Joseph C Maranville; Zhenqiu Liu; Shannon Ellis; Pankaj Chopra; Jonathan S Alexander; Robert N Baldassano; Raymond K Cross; Themistocles Dassopoulos; Tanvi A Dhere; Richard H Duerr; John S Hanson; Jason K Hou; Sunny Z Hussain; Kim L Isaacs; Kelly E Kachelries; Howard Kader; Michael D Kappelman; Jeffrey Katz; Richard Kellermayer; Barbara S Kirschner; John F Kuemmerle; Archana Kumar; John H Kwon; Mark Lazarev; Peter Mannon; Dedrick E Moulton; Bankole O Osuntokun; Ashish Patel; John D Rioux; Jerome I Rotter; Shehzad Saeed; Ellen J Scherl; Mark S Silverberg; Ann Silverman; Stephan R Targan; John F Valentine; Ming-Hsi Wang; Claire L Simpson; S Louis Bridges; Robert P Kimberly; Stephen S Rich; Judy H Cho; Anna Di Rienzo; Linda W H Kao Journal: Gastroenterology Date: 2015-08-14 Impact factor: 22.682
Authors: David Prescott; Charles Maisonneuve; Jitender Yadav; Stephen J Rubino; Stephen E Girardin; Dana J Philpott Journal: Proc Natl Acad Sci U S A Date: 2020-04-29 Impact factor: 11.205
Authors: Yolanda F M Tolentino; Paula Peruzzi Elia; Homero Soares Fogaça; Antonio José V Carneiro; Cyrla Zaltman; Rodrigo Moura-Neto; Ronir Raggio Luiz; Maria da Gloria C Carvalho; Heitor S de Souza Journal: Dig Dis Sci Date: 2016-04-23 Impact factor: 3.199
Authors: E N Ngoh; H K Brugger; M Monajemi; S C Menzies; A F Hirschfeld; K L Del Bel; K Jacobson; P M Lavoie; S E Turvey; L M Sly Journal: Genes Immun Date: 2015-07-30 Impact factor: 2.676