title: NELL1, NCF4, and FAM92B genes are not major susceptibility genes for Crohn's disease in Canadian children and young adults.
abstract: BACKGROUND
  Genome-wide association studies (GWAS) and replication studies have shown conflicting associations between the NELL1, NCF4, and FAM92B genes and susceptibility for Crohn's disease (CD). We sought to examine whether these genes were associated with CD in Canadian children and young adults.
  
  
  METHODS
  A case-control study was carried out at three pediatric gastroenterology clinics across Canada. Patients, ≤20 years at diagnosis, along with controls representative of the general population were selected. Study subjects were genotyped for 22 single nucleotide polymorphisms (SNPs) across the target genes. Allelic and haplotype associations were examined. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated.
  
  
  RESULTS
  In all, 566 CD cases and 602 controls were investigated. The mean (±SD) age of the patients was 12.3 (±3.3) years. Most patients were male (57.8%), of Caucasian ancestry (98.2%), and had ileocolonic disease location (48.8%). Barring nominal associations with one FAM92B SNP, none of the other 21 SNPs analyzed were associated with CD either at the allelic or haplotype level. Separate analysis for ileal CD (L1 plus L3) also did not reveal significant associations with any of the SNPs. Similarly, a pooled analysis using data from two recent studies did not demonstrate associations between the NCF4 (OR = 1.10, 95% CI = 0.91-1.32, P = 0.32) and FAM92B (OR = 1.05, 95% CI = 0.95-1.17, P = 0.36) GWAS lead SNPs and ileal CD.
  
  
  CONCLUSIONS
  GWAS-reported associations in the NELL1, NCF4, and FAM92B genes could not be replicated in Canadian children and young adults. Further investigation in other populations will be required to confirm the presence/absence of associations, if any.
authors.affiliation: Department of Pediatrics, University of Montreal, Montreal, Canada; Research Centre, Sainte-Justine Hospital, Montreal, Canada. devendra.amre@umontreal.ca
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Amre
authors.forename: David R
authors.initials: DR
authors.lastname: Mack
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: Emile
authors.initials: E
authors.lastname: Levy
mesh_terms: D000293:Adolescent; D000483:Alleles; D002135:Calcium-Binding Proteins; D002170:Canada; D016022:Case-Control Studies; D002648:Child; D016001:Confidence Intervals; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D007077:Ileal Diseases / Q000235:genetics; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
chemical_list: C572790:CIBAR2 protein, human; D002135:Calcium-Binding Proteins; C104144:NELL1 protein, human; D009419:Nerve Tissue Proteins; D011506:Proteins; D019255:NADPH Oxidases; C113333:NCF4 protein, human