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Genetic association of the autophagy genes, autophagy-related 16-like 1 (ATG16L1) and immunity-related GTPase family, M (IRGM), has been confirmed by meta-analysis of three index genome-wide association studies (GWASs), and in other independent studies in adult-onset Crohn’s disease, but not ulcerative colitis.1–5 While the meta-analysis implicated a single nucleotide polymorphism (SNP; rs11747270) based on imputed data from the constituent GWAS with odds ratio (OR) 1.33, other studies have replicated the IRGM signal based on rs13361189 and rs4958847. Recently, rs13361189, upstream of IRGM, was shown to be in perfect linkage disequilibrium with a 20 kb deletion polymorphism affecting the expression of IRGM (and cellular autophagy) in a tissue-specific manner.5
We read with interest the letter by Peterson et al (Gut 2008;57:1336–7) which suggested association of IRGM with childhood-onset Crohn’s disease in a North American cohort. Only one of the two IRGM variants studied (rs13361189) was weakly associated with Crohn’s disease in their study …
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