IRGM variants and susceptibility to inflammatory bowel disease in the German population.

Genome-wide association studies identified the autophagy gene IRGM
to be strongly associated with Crohn's disease (CD) but its impact
in ulcerative colitis (UC), its phenotypic effects and potential
epistatic interactions with other IBD susceptibility genes are less
clear which we therefore analyzed in this study. Genomic DNA from
2060 individuals including 817 CD patients, 283 UC patients, and
961 healthy, unrelated controls (all of Caucasian origin) was
analyzed for six IRGM single nucleotide polymorphisms (SNPs)
(rs13371189, rs10065172 = p.Leu105Leu, rs4958847, rs1000113,
rs11747270, rs931058). In all patients, a detailed
genotype-phenotype analysis and testing for epistasis with the
three major CD susceptibility genes NOD2, IL23R and ATG16L1 were
performed. Our analysis revealed an association of the IRGM SNPs
rs13371189 (p = 0.02, OR 1.31 [95% CI 1.05-1.65]), rs10065172 =
p.Leu105Leu (p = 0.016, OR 1.33 [95% CI 1.06-1.66]) and rs1000113
(p = 0.047, OR 1.27 [95% CI 1.01-1.61]) with CD susceptibility.
There was linkage disequilibrium between these three IRGM SNPs. In
UC, several IRGM haplotypes were weakly associated with UC
susceptibility (p