title: Genetic susceptibility and genotype-phenotype association in 588 Danish children with inflammatory bowel disease.
abstract: OBJECTIVE
  To investigate the association between known inflammatory bowel disease (IBD)-associated genetic variants and development of paediatric IBD, and specific clinical sub-phenotypes.
  
  
  METHODS
  In this case-control study we included IBD patients <18 years of age at diagnosis from the Danish National Patient Registry and healthy children <18 years of age were randomly selected from the Danish Central Office of Civil Registration. The latter had filled out a questionnaire regarding health status, and DNA was obtained from blood samples and the buccal mucosa. Patient files were retrieved and clinical information was extracted. DNA was obtained from Guthrie cards from the Danish National Neonatal Screening Biobank (PKU-biobanken) at Statens Serum Institut and from blood samples.
  
  
  RESULTS
  A total of 588 IBD patients (244 Crohn's disease (CD), 318 ulcerative colitis (UC) and 26 IBD-unclassified (IBDU)) and 543 healthy controls were included. We found an association between CD and rs22411880 (ATG16L1, odds ratio (OR)=1.7 [1.1-1.7], p=0.003), rs5743289 (NOD2, OR=1.4 [1.1-1.9], p=0.009) and the paediatric specific rs1250550 (ZMIZ1, OR=0.7 [0.5-0.9], p=0.01). None of the investigated 41 SNPs were associated with disease localisation, medical treatment or surgery after correcting for multiple analyses.
  
  
  CONCLUSIONS
  We found an association between CD and three previously published genetic variants and replicated the association with the paediatric specific ZMIZ1 gene. No Bonferroni corrected significant genotype-phenotype associations were found. For future studies aimed at finding predictors for disease course in (paediatric) IBD, it will be worthwhile to include a combination of genetic, clinical and serological markers.
authors.affiliation: Department of Paediatrics, Hvidovre University Hospital, Copenhagen, Denmark. Electronic address: Christian.jakobsen.03@regionh.dk.
authors.forename: C
authors.initials: C
authors.lastname: Jakobsen
authors.affiliation: Department of Clinical and Experimental Medicine, KU Leuven, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Cleynen
authors.affiliation: Department of Microbiology and Infection Control, State Serum Institute, Copenhagen, Denmark.
authors.forename: P S
authors.initials: PS
authors.lastname: Andersen
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev University Hospital, Copenhagen, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Munkholm
authors.affiliation: Department of Paediatrics, Hvidovre University Hospital, Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Paerregaard
authors.affiliation: Department of Paediatrics, Hvidovre University Hospital, Copenhagen, Denmark.
authors.forename: V
authors.initials: V
authors.lastname: Wewer
mesh_terms: D000293:Adolescent; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000235:genetics*; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics*; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D014157:Transcription Factors; C480599:ZMIZ1 protein, human
keywords: Crohn's disease; Epidemiology; Genotype; Phenotype; Ulcerative colitis