BACKGROUND & AIMS: Crohn's disease is an inflammatory bowel disease induced by multiple genetic and environmental factors. Genome-wide association studies have identified genetic factors that affect the risk for Crohn's disease in European populations, but information from other ethnic groups is scarce. We therefore investigated genetic factors associated with Crohn's disease in the Japanese population. METHODS: We performed a genome-wide association study with 372 individuals with Crohn's disease (cases) and 3389 controls, all from the Japanese population. To confirm identified associations, we performed a replication study with an independent panel of 1151 Crohn's disease cases and 15,800 controls. We also performed an association analysis using genome-wide genotype imputation in the discovery cohort. RESULTS: We confirmed associations of Crohn's disease with variants in MHC (rs7765379, P = 2.11 × 10(-59)), TNFSF15 (rs6478106, P = 3.87 × 10(-45)), and STAT3 (rs9891119, P = 2.24 × 10(-14)). We identified 2 new susceptibility loci: on chromosome 4p14 (rs1487630, P = 2.40 × 10(-11); odds ratio, 1.33), and in the SLC25A15-ELF1-WBP4 region on 13q14 (rs7329174 in ELF1, P = 5.12 × 10(-9); odds ratio, 1.27). CONCLUSIONS: In a genome-wide association study, we identified 2 new susceptibility loci for Crohn's disease in a Japanese population. These findings could increase our understanding of the pathogenesis of Crohn's disease.
BACKGROUND & AIMS:Crohn's disease is an inflammatory bowel disease induced by multiple genetic and environmental factors. Genome-wide association studies have identified genetic factors that affect the risk for Crohn's disease in European populations, but information from other ethnic groups is scarce. We therefore investigated genetic factors associated with Crohn's disease in the Japanese population. METHODS: We performed a genome-wide association study with 372 individuals with Crohn's disease (cases) and 3389 controls, all from the Japanese population. To confirm identified associations, we performed a replication study with an independent panel of 1151 Crohn's disease cases and 15,800 controls. We also performed an association analysis using genome-wide genotype imputation in the discovery cohort. RESULTS: We confirmed associations of Crohn's disease with variants in MHC (rs7765379, P = 2.11 × 10(-59)), TNFSF15 (rs6478106, P = 3.87 × 10(-45)), and STAT3 (rs9891119, P = 2.24 × 10(-14)). We identified 2 new susceptibility loci: on chromosome 4p14 (rs1487630, P = 2.40 × 10(-11); odds ratio, 1.33), and in the SLC25A15-ELF1-WBP4 region on 13q14 (rs7329174 in ELF1, P = 5.12 × 10(-9); odds ratio, 1.27). CONCLUSIONS: In a genome-wide association study, we identified 2 new susceptibility loci for Crohn's disease in a Japanese population. These findings could increase our understanding of the pathogenesis of Crohn's disease.
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: William V Perks; Ravinder K Singh; Gareth W Jones; Jason P Twohig; Anwen S Williams; Ian R Humphreys; Philip R Taylor; Simon A Jones; Eddie C Y Wang Journal: Am J Pathol Date: 2016-09-21 Impact factor: 4.307