BACKGROUND & AIMS: There are many genetic factors that are associated with both ulcerative colitis (UC) and Crohn's disease (CD). However, genetic factors that have distinct effects on UC and CD have not been examined. METHODS: We performed a comparative genome-wide association study (GWAS) and a replication study using data from 748 patients with UC and 979 with CD, selected from a Japanese population. We conducted high-resolution (4-digit) genotyping of human leukocyte antigen (HLA) alleles in patients with UC and CD and additional 905 healthy individuals (controls). We performed haplotype-based analysis using data from the GWAS and HLA alleles to associate them with UC or CD. RESULTS: The comparative GWAS and the replication study identified significant associations in the major histocompatibility complex region at 6p21 with UC and CD (rs9271366, P = 1.6 × 10⁻⁷⁰; odds ratio [OR] = 4.44). Haplotype-based analysis in the major histocompatibility complex region showed that HLA-Cw*1202-B*5201-DRB1*1502 haplotype was significantly associated with increased risk of UC compared with CD (P = 1.1 × 10⁻³³; OR = 6.58), accounting for most of the associations observed in the GWAS. Compared with the controls, this HLA haplotype significantly increases susceptibility to UC (P = 4.0 × 10⁻²¹; OR = 2.65), but reduces risk for CD (P = 1.1 × 10⁻⁷; OR = 0.40). Distinct effects of this HLA haplotype on UC and CD were independent of other HLA alleles and haplotypes (P = 2.0 × 10⁻¹⁹ and P = 7.2 × 10⁻⁵, respectively). CONCLUSIONS: The HLA-Cw*1202-B*5201-DRB1*1502 haplotype increases susceptibility to UC but reduces risk for CD, based on a GWAS of a Japanese population.
BACKGROUND & AIMS: There are many genetic factors that are associated with both ulcerative colitis (UC) and Crohn's disease (CD). However, genetic factors that have distinct effects on UC and CD have not been examined. METHODS: We performed a comparative genome-wide association study (GWAS) and a replication study using data from 748 patients with UC and 979 with CD, selected from a Japanese population. We conducted high-resolution (4-digit) genotyping of human leukocyte antigen (HLA) alleles in patients with UC and CD and additional 905 healthy individuals (controls). We performed haplotype-based analysis using data from the GWAS and HLA alleles to associate them with UC or CD. RESULTS: The comparative GWAS and the replication study identified significant associations in the major histocompatibility complex region at 6p21 with UC and CD (rs9271366, P = 1.6 × 10⁻⁷⁰; odds ratio [OR] = 4.44). Haplotype-based analysis in the major histocompatibility complex region showed that HLA-Cw*1202-B*5201-DRB1*1502 haplotype was significantly associated with increased risk of UC compared with CD (P = 1.1 × 10⁻³³; OR = 6.58), accounting for most of the associations observed in the GWAS. Compared with the controls, this HLA haplotype significantly increases susceptibility to UC (P = 4.0 × 10⁻²¹; OR = 2.65), but reduces risk for CD (P = 1.1 × 10⁻⁷; OR = 0.40). Distinct effects of this HLA haplotype on UC and CD were independent of other HLA alleles and haplotypes (P = 2.0 × 10⁻¹⁹ and P = 7.2 × 10⁻⁵, respectively). CONCLUSIONS: The HLA-Cw*1202-B*5201-DRB1*1502 haplotype increases susceptibility to UC but reduces risk for CD, based on a GWAS of a Japanese population.
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: Jun Wang; Louise B Thingholm; Jurgita Skiecevičienė; Philipp Rausch; Martin Kummen; Johannes R Hov; Frauke Degenhardt; Femke-Anouska Heinsen; Malte C Rühlemann; Silke Szymczak; Kristian Holm; Tönu Esko; Jun Sun; Mihaela Pricop-Jeckstadt; Samer Al-Dury; Pavol Bohov; Jörn Bethune; Felix Sommer; David Ellinghaus; Rolf K Berge; Matthias Hübenthal; Manja Koch; Karin Schwarz; Gerald Rimbach; Patricia Hübbe; Wei-Hung Pan; Raheleh Sheibani-Tezerji; Robert Häsler; Philipp Rosenstiel; Mauro D'Amato; Katja Cloppenborg-Schmidt; Sven Künzel; Matthias Laudes; Hanns-Ulrich Marschall; Wolfgang Lieb; Ute Nöthlings; Tom H Karlsen; John F Baines; Andre Franke Journal: Nat Genet Date: 2016-10-10 Impact factor: 38.330