title: A population-based case-control study of CARD15 and other risk factors in Crohn's disease and ulcerative colitis.
abstract: OBJECTIVE
  Multiple established Crohn's disease (CD) and ulcerative colitis (UC) risk factors including family history, tobacco use, Jewish ethnicity, urban residency, and CARD15/NOD2 mutations have been evaluated singly and in hospital-based observational studies. The goal of this study was to assess the relative contributions of all these risk factors jointly in a nonreferral, population-based cohort derived from a population epidemiologic database.
  
  
  METHODS
  CD (N = 232) and UC (N = 121) subjects were ascertained from our population-based IBD Registry derived from Manitoba Health, the single provincial insurer. Healthy controls (HC) (N = 336) were recruited via a 10:1 mailing matched for age, sex, and postal code. Ethnicity, tobacco use, family history, residency, and CARD15/NOD2 genotype status were determined.
  
  
  RESULTS
  In both univariate analyses and analyses adjusted for all risk factors, CD was influenced independently by CARD15/NOD2 heterozygote and homozygote/compound-heterozygote status (adjusted odds ratios [OR] 3.7 and 40.0, respectively), Jewish ethnicity (OR 18.5), CD family history (OR 6.2), and smoking (OR 3.0 current and 1.7 ex-smoker, respectively). Penetrance for homozygote/compound-heterozygotes was 4.9%, heterozygotes 0.54%, and wild types 0.184%. Population attributable risk for CARD15 was 26.7% and current tobacco use was 46.8%. A tobacco-CARD15 interaction was not observed. UC was influenced by Jewish ethnicity (OR 37.1), and by family history (OR 2.6), ex-smoker status (OR 1.9), and CARD15/NOD2 heterozygote or homozygote/compound-heterozygote status (OR 1.9 and 6.4, respectively) in adjusted analyses only.
  
  
  CONCLUSIONS
  CARD15/NOD2, family history, smoking, and Jewish ethnicity are independent risk factors for CD. Examination of these risk factors together in a single population-based cohort has provided initial data for population epidemiological characterization and genetic counseling uses.
authors.affiliation: Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Brant
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Wang
authors.forename: Patricia
authors.initials: P
authors.lastname: Rawsthorne
authors.forename: Michael
authors.initials: M
authors.lastname: Sargent
authors.forename: Lisa Wu
authors.initials: LW
authors.lastname: Datta
authors.forename: Franklin
authors.initials: F
authors.lastname: Nouvet
authors.forename: Yin Yao
authors.initials: YY
authors.lastname: Shugart
authors.forename: Charles N
authors.initials: CN
authors.lastname: Bernstein
mesh_terms: D000293:Adolescent; D000328:Adult; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics*; D003424:Crohn Disease / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007585:Jews; D008297:Male; D008350:Manitoba / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011159:Population Surveillance; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014505:Urban Population
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D004247:DNA