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GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach. [ABSTRACT FROM AUTHOR]

The inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. Enormous progress has been made recently in understanding the pathogenesis of these diseases. Through the study of patients and mouse models, it has emerged that Crohn's disease is driven by the production of interleukin-12 (IL-12) and interferon-? (IFN-?), whereas ulcerative colitis is probably driven by the production of IL-13. A second area of progress is in the identification of specific genetic abnormalities that are responsible for disease. The most important finding is the identification of mutations in the gene that encodes NOD2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. Here, we discuss these recent findings and the implications for therapy. [ABSTRACT FROM AUTHOR]

Studies the allele frequencies of the codon 10 and the codon 25 transforming growth factor-β (TGFB) gene polymorphism in a Dutch population of inflammatory bowel disease (IBD) patients. Importance of TGF-&beta in maintaining intestinal immune homeostasis; Likelihood of the anti-inflammatory and immunosuppressive effects of TGF-&beta1 to offer important potential physiological and therapeutic applications; Irrelevance of the codon 10 and codon 15 TGFB1 gene polymorphism in defining the susceptibility to and the nature of the clinical course of IBD.

A letter to the editor is presented in response to the article on the uneventful recovery of 40-year old patient having post-colonoscopy massive air leakage with full body involvement.