title: Influence of Crohn's disease risk alleles and smoking on disease location.
abstract: OBJECTIVE
  : Our objective is to assess the effect of genetic and environmental factors on Crohn's disease location.
  
  
  METHODS
  : We identified 628 patients with Crohn's disease within the Washington University database (April 2005 through February 2010) that had complete information on 31 Crohn's disease-associated genotypes and clinical information on disease location (L1 to L4), smoking, sex, race, and age at diagnosis. For statistical reasons, the 3 major NOD2 alleles (rs2066844, rs2066845, and rs2066847) were grouped together. Logistic regression incorporating all of the genotypes and clinical covariates, including smoking, was performed with stepwise variable selection and by best subset selection.
  
  
  RESULTS
  : Stepwise variable selection selected 3 major covariates, composite NOD2 genotype, smoking, and TNFSF15 genotype, which are also the 3 covariates selected by the best subset method. Whereas the NOD2 genotype and smoking are positively associated with ileal (L1 + L3) disease, the TNFSF15 genotype is positively associated with isolated colonic (L2) disease.
  
  
  CONCLUSIONS
  : The ability to detect disease site associations in this single-center study may be limited by the population size, low allelic frequency, and/or low odds ratio of certain Crohn's disease risk alleles.
  
  
  CONCLUSIONS
  : These results indicate that NOD2 genotype, smoking status, and TNFSF15 genotype should be included as covariates in assessing the effect of genetic and environmental factors on Crohn's disease site location.
authors: Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors: Hongyan
authors: H
authors: Chen
authors: Alexander
authors: A
authors: Lee
authors: Anne
authors: A
authors: Bowcock
authors: Wei
authors: W
authors: Zhu
authors: Ellen
authors: E
authors: Li
authors: Matthew
authors: M
authors: Ciorba
authors: Steven
authors: S
authors: Hunt
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D003108:Colonic Diseases / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007077:Ileal Diseases / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D012907:Smoking; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics*; D055815:Young Adult
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15