Rs2241880

rs2241880, a SNP in the ATG16L1 gene encoding a threonine to alanine substitution ("T300A") in a protein known to be involved in the function of the epithelial cells lining the intestine, has been associated with Crohn's disease in several recent studies. [PMID 17200669, PMID 17435756]

In another recent (2007) report, rs2241880 is confirmed to be associated with both Crohn's disease and ileal disease, but additionally, the authors calculate risk for individuals who are homozygotes for this SNP plus 2 others (in the IBD5 and NOD2 genes). Individuals homozygous for the risk alleles for all 3 of these SNPs are estimated to be at 20 fold higher risk (CI ~9-49) for Crohn's disease. [PMID 17484864] From the largest most recent survey, the Crohn's disease-associated SNPs for IBD5 and NOD2 are, respectively, rs6596075 and rs17221417. [PMID 17554300]

[PMID 18047540] associated With Inflammatory Bowel Diseases but Not With Celiac Disease rs11209026 had a protective effect for IBD in the case-control analysis (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.10-0.37, P= 6.6E-09). Both CD (OR 0.14, CI 0.06-0.37, P= 3.9E-07) and UC (OR 0.33, CI 0.15-0.73, P= 1.4E-03) were associated with IL23R. rs2241880 was associated with CD susceptibility (OR 1.36, CI 1.12-1.66, P= 0.0017). The population-attributable risk of carrying allele G is 0.24 and is 0.19 for homozygosity for allele G in CD.

In another study, rs2241880 has been associated with Crohn's disease; the minor allele is somewhat protective in that it lessens the odds of acquiring the disease (odds ratio 0.74, CI: 0.65-0.84, p=3.7x10e-6).[PMID 18162085]

[PMID 18366306] Review of role of rs2241880 in Crohn's disease and possibly ulcerative colitis

[PMID 18698678] Replicated increased risk for Crohn's disease with rs2241880(C) allele in a study of Italian patients, but saw no association to ulcerative colitis (UC).

[PMID 18985712] strongly associated with ileal Crohn's disease (allelic P = 1.24 x 10(-6)). Children with GG genotype had a more than 3-fold elevated risk for disease as compared to the wildtype AA homozygotes (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.93-4.94; P = 1.8 x 10(-6))

[PMID 19337756] Meta-analysis of 24 studies performed, including 13,022 Crohn's disease cases and 17,532 controls. Confirmed increased risk for disease for carriers of (C) allele (1.9x or 1.4x, for homozygous and heterozgous genotypes), but only in Caucasians and not in Asians.

[PMID 19491842] Study of 557 CD and 425 UC patients and 672 ethnically matched Spanish controls and a meta-analysis confirmed an association between rs2241880(C) and CD (p=6.5 x 10(-9), odds ratio =1.62).

GWAS
SNP	rs2241880
PubMedID	[PMID 17435756]
Condition	Crohn's disease
Gene	ATG16L1
Risk Allele	G
pValue	1.00E-013
OR	1.45
95% CI	1.27-1.64

[PMID 19174780] Confirmation of multiple Crohn's disease susceptibility loci in a large Dutch-Belgian cohort

[PMID 19575361] Role of ATG16L1 Thr300Ala polymorphism in inflammatory bowel disease: A Study in the Spanish population and a meta-analysis

[PMID 19590455] Association of IL23R p.381Gln and ATG16L1 p.197Ala With Crohn Disease in the Czech Population

[PMID 20380008] NOD2/CARD15, ATG16L1 and IL23R gene polymorphisms and childhood-onset of Crohn's disease

[PMID 20485703] Replication and meta-analysis of 13,000 cases defines the risk for interleukin-23 receptor and autophagy-related 16-like 1 variants in Crohn's disease

GWAS snp
PMID	[PMID 20570966]
Trait	Crohn's disease
Title	Fucosyltransferase 2(FUT2) Non-Secretor Status is associated with Crohn's Disease
Risk Allele
P-val	0.000003
Odds Ratio	1.32 [1.18-1.47]

[PMID 21206965] IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes

[PMID 21513755] ATG16L1 gene polymorphisms are associated with palmoplantar pustulosis

[PMID 22115380] Prediction of disease complication occurrence in Crohn's disease using phenotype and genotype parameters at diagnosis

[PMID 22457781] PTPN2 Gene Variants Are Associated with Susceptibility to Both Crohn's Disease and Ulcerative Colitis Supporting a Common Genetic Disease Background