title: HLA-Cw*1202-B*5201-DRB1*1502 haplotype increases risk for ulcerative colitis but reduces risk for Crohn's disease.
abstract: OBJECTIVE
  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.affiliation: Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Yokohama Institute, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Okada
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Junji
authors.initials: J
authors.lastname: Umeno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Natsuhiko
authors.initials: N
authors.lastname: Kumasaka
authors.forename: Kyota
authors.initials: K
authors.lastname: Ashikawa
authors.forename: Tomomi
authors.initials: T
authors.lastname: Aoi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takazoe
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsui
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirano
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D003424:Crohn Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D059950:HLA-B52 Antigen / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: C501279:HLA-B*52:01 antigen; D059950:HLA-B52 Antigen; D015236:HLA-C Antigens; D059811:HLA-DRB1 Chains