title: Distinct and overlapping genetic loci in Crohn's disease and ulcerative colitis: correlations with pathogenesis.
abstract: BACKGROUND
  A common genotypic basis for ulcerative colitis (UC) and Crohn's disease (CD) is implied by overlapping clinical characteristics, epidemiological studies, and association of genes with both UC and CD. We evaluated the overlap between CD and UC genetic loci stratified by pathogenetic pathways and by disease location.
  
  
  METHODS
  The allele frequencies of six UC-associated and 34 CD-associated single nucleotide polymorphisms (SNPs) were determined in a Canadian IBD cohort (n = 2374). Differences between CD, UC, colon-only CD, ileal CD, and controls were analyzed controlling for ethnicity, age of diagnosis, and gender.
  
  
  RESULTS
  In all, 21 of 34 CD-associated SNPs had similar allele frequencies in UC (n = 1230) and CD (n = 1144). Three of six UC-associated SNPs had significantly different frequencies in CD (n = 1144). Most of the divergence in allele frequency among CD and UC was noted in NOD2/autophagy pathway SNPs, while most SNPs with similar frequencies were in IL-22/23 Th17, adaptive immunity, and barrier pathways. Colon-only CD (n = 228) was compared with healthy controls: three of six UC SNPs (in MST1, HLA-DRA, and IL-23R) and 11 of 34 CD SNPs: in IRGM, NOD2 (rs2066845), CCNY, MST1, IL23R, PTPN22, C11orf30, ZNF365, PTPN2, PSMG1, and rs1456893 were significantly associated. In all, 29 of 34 CD SNPs had similar allele frequencies in colonic CD compared with ileal CD (n = 366). All UC SNPs had similar frequencies in UC and colonic CD.
  
  
  CONCLUSIONS
  Our results suggest that CD and UC share common genetic associations related to impaired adaptive immunity and diverge in pathways of foreign antigen processing. Colon-only CD overlaps extensively with UC and considerably with ileal CD.
authors.affiliation: Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital IBD Group, Toronto, ON, Canada.
authors.forename: Matti
authors.initials: M
authors.lastname: Waterman
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Stempak
authors.forename: Raquel
authors.initials: R
authors.lastname: Milgrom
authors.forename: Charles N
authors.initials: CN
authors.lastname: Bernstein
authors.forename: Anne M
authors.initials: AM
authors.lastname: Griffiths
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Greenberg
authors.forename: A Hillary
authors.initials: AH
authors.lastname: Steinhart
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis* / Q000378:metabolism; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004247:DNA