Confirmation of the role of ATG16L1 as a Crohn's disease susceptibility gene

J. R Fraser Cummings, Rachel Cooney, Saad Pathan, Carl A. Anderson, Jeffrey C. Barrett, John Beckly, Alexandra Geremia, Laura Hancock, Changcun Guo, Tariq Ahmad, Ion R. Cardon, Derek P. Jewell

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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 rs2241880 and was confirmed in 2 German independent case-control collections (combined P = 4.0 × 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 (1049). The nsSNP rs2241880 was genotyped using MassArray (Sequenom). Results: A strong association with CD was demonstrated (P = 2.33 × 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 rs2241880 and the CARD 15 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.

Original languageEnglish
Pages (from-to)941-946
Number of pages6
JournalInflammatory Bowel Diseases
Issue number8
Publication statusPublished - Aug 2007
Externally publishedYes



  • ATG16L1
  • CARD15
  • Crohn's disease
  • Interaction
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Cummings, J. R. F., Cooney, R., Pathan, S., Anderson, C. A., Barrett, J. C., Beckly, J., Geremia, A., Hancock, L., Guo, C., Ahmad, T., Cardon, I. R., & Jewell, D. P. (2007). Confirmation of the role of ATG16L1 as a Crohn's disease susceptibility gene. Inflammatory Bowel Diseases, 13(8), 941-946.