title: Confirmation of the role of ATG16L1 as a Crohn's disease susceptibility gene.
abstract: BACKGROUND
  A German genome-wide nonsynonymous single nucleotide polymorphism (nsSNP) association study identified ATG16L1 as a Crohn's disease (CD) susceptibility gene. The association appeared to be confined to the nsSNP rs2,241,880 and was confirmed in 2 German independent case-control collections (combined P = 4.0 x 10(-8), odds ratio [OR] 1.45; 95% confidence interval [CI]: 1.21-1.74), a CD transmission disequilibrium test (TDT) collection, and an independent UK cohort. A weak statistical interaction with CARD15 was demonstrated. No association with ulcerative colitis (UC) was demonstrated. The aims of the study were to replicate the association with CD, examine subphenotype associations and statistical interactions with CARD15, IL23R, and the IBD5 risk haplotype, as well as explore the association with UC.
  
  
  METHODS
  The study included 645 CD and 676 UC rigorously phenotyped patients recruited from a single UK center. Unaffected controls comprised either spouses of patients (141) or individuals recruited from well-person clinics (1,049). The nsSNP rs2,241,880 was genotyped using MassArray (Sequenom).
  
  
  RESULTS
  A strong association with CD was demonstrated (P = 2.33 x 10(-7), OR 1.45 [1.25-1.67]), but no significant association was demonstrated with any subphenotype. We failed to replicate the reported interaction between rs2,241,880 and the CARD15 low-risk haplotypes dd and Dd. No significant statistical interaction with the 3 known CD susceptibility genes was seen. No association with UC susceptibility (P = 0.37, OR 1.06 [0.93-1.22]), or any UC subphenotype was identified.
  
  
  CONCLUSIONS
  We confirmed the findings that ATG16L1 is a CD susceptibility gene and found no evidence of interaction with CARD15, IL23R, or IBD5.
authors: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. fraserc@well.ox.ac.uk
authors: J R Fraser
authors: JR
authors: Cummings
authors: Rachel
authors: R
authors: Cooney
authors: Saad
authors: S
authors: Pathan
authors: Carl A
authors: CA
authors: Anderson
authors: Jeffrey C
authors: JC
authors: Barrett
authors: John
authors: J
authors: Beckly
authors: Alessandra
authors: A
authors: Geremia
authors: Laura
authors: L
authors: Hancock
authors: Changcun
authors: C
authors: Guo
authors: Tariq
authors: T
authors: Ahmad
authors: Lon R
authors: LR
authors: Cardon
authors: Derek P
authors: DP
authors: Jewell
mesh_terms: D000293:Adolescent; D000328:Adult; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C515500:IL23R protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin