title: Genome-wide association study signal at the 12q12 locus for Crohn's disease may represent associations with the MUC19 gene.
abstract: BACKGROUND
  Genome-wide association studies (GWAS) in Crohn's disease (CD) have identified associations with single-nucleotide polymorphism (SNP) rs11175593 at chromosome 12q12. The MUC19 and LRRK2 genes reside close to the GWAS signal, but it is as yet unclear which of the 2 genes represent the CD susceptibility genes.
  
  
  METHODS
  We studied associations between nonsynonymous coding variants in the MUC19 (5) and LRRK2 (3) genes in a case-control sample comprising CD cases aged <18 years at diagnosis. The GWAS lead SNP rs11175593 was also investigated. Allelic, genotype, and haplotype associations were examined assuming different models of inheritance.
  
  
  RESULTS
  A total of 530 cases and 600 controls were studied. The mean (±SD) age at diagnosis was 12.4 (±3.3). Most cases were male (57.4%). Most patients had ileocolonic disease location (48.8%) and inflammatory behavior at diagnosis (87.0%). Three MUC19 SNPs were nominally significantly associated with CD (rs11564245, Asp→His: P = 0.02; rs4768261, Ser→Phe: P = 0.0008; and rs2933353, Glu→Ala: P = 0.01). Associations with rs4768261 were maintained after corrections for multiple comparisons (permuted, P = 0.007). None of the LRRK2 SNPs were associated with CD. Haplotype analysis supported the single SNP associations noted with the MUC19 gene.
  
  
  CONCLUSIONS
  GWAS signal at chromosome 12q12 for CD may represent associations with the MUC19 gene.
authors.affiliation: Division of Gastroenterology, Hepatology & Nutrition, Research Centre, CHU-Ste-Justine, Montreal, Canada.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.forename: David R
authors.initials: DR
authors.lastname: Mack
authors.forename: Valerie
authors.initials: V
authors.lastname: Marcil
authors.forename: David
authors.initials: D
authors.lastname: Israel
authors.forename: Alfreda
authors.initials: A
authors.lastname: Krupoves
authors.forename: Irina
authors.initials: I
authors.lastname: Costea
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambrette
authors.forename: Guy
authors.initials: G
authors.lastname: Grimard
authors.forename: Jinsong
authors.initials: J
authors.lastname: Dong
authors.forename: Ernest G
authors.initials: EG
authors.lastname: Seidman
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Amre
authors.forename: Emile
authors.initials: E
authors.lastname: Levy
mesh_terms: D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D009077:Mucins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors
chemical_list: C482349:MUC19 protein, human; D009077:Mucins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases