10.1371/journal.pone.0054338 Jürgen Glas Jürgen Glas Julia Seiderer Julia Seiderer Stephanie Bues Stephanie Bues Johannes Stallhofer Johannes Stallhofer Christoph Fries Christoph Fries Torsten Olszak Torsten Olszak Eleni Tsekeri Eleni Tsekeri Martin Wetzke Martin Wetzke Florian Beigel Florian Beigel Christian Steib Christian Steib Matthias Friedrich Matthias Friedrich Burkhard Göke Burkhard Göke Julia Diegelmann Julia Diegelmann Darina Czamara Darina Czamara Stephan Brand Stephan Brand <em>IRGM</em> Variants and Susceptibility to Inflammatory Bowel Disease in the German Population Public Library of Science 2013 variants susceptibility inflammatory bowel german population 2013-01-24 01:10:46 Dataset https://plos.figshare.com/articles/dataset/_IRGM_Variants_and_Susceptibility_to_Inflammatory_Bowel_Disease_in_the_German_Population__/154246 <div><h3>Background & Aims</h3><p>Genome-wide association studies identified the autophagy gene <em>IRGM</em> 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.</p> <h3>Methodology/Principal Findings</h3><p>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 <em>IRGM</em> 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 <em>NOD2</em>, <em>IL23R</em> and <em>ATG16L1</em> were performed.</p> <p>Our analysis revealed an association of the <em>IRGM</em> 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 <em>IRGM</em> SNPs. In UC, several <em>IRGM</em> haplotypes were weakly associated with UC susceptibility (p<0.05). Genotype-phenotype analysis revealed no significant associations with a specific IBD phenotype or ileal CD involvement. There was evidence for weak gene-gene-interaction between several SNPs of the autophagy genes <em>IRGM</em> and <em>ATG16L1</em> (p<0.05), which, however, did not remain significant after Bonferroni correction.</p> <h3>Conclusions/Significance</h3><p>Our results confirm <em>IRGM</em> as susceptibility gene for CD in the German population, supporting a role for the autophagy genes <em>IRGM</em> and <em>ATG16L1</em> in the pathogenesis of CD.</p> </div>