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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Autoimmune Diseases, Colitis, Ulcerative, Crohn Disease, Cytokines, Databases, Genetic, Epidermal Growth Factor, European Continental Ancestry Group, Gene Ontology, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Intercellular Signaling Peptides and Proteins, Protein Interaction Domains and Motifs, Protein Interaction Mapping, Quantitative Trait Loci, Receptors, Cytokine, STAT Transcription Factors, Signal Transduction.
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Do pathway-based Genome-wide Association Studies Reveal the Association Between Growth Factor Activity and Inflammatory Bowel Disease? Context: The inflammatory bowel diseases known as Crohn's disease (CD) and ulcerative colitis (UC) are related autoimmune conditions with a complex etiology composed of genetic and environmental factors. Genetic studies have revealed 200 susceptibility loci for inflammatory bowel diseases, but these only account for a small fraction of the genetic heritability of the disease. We employed pathway-based approaches to identify genes that cooperatively make contributions to the genetic etiology of CD. We exploited the largest CD dataset (20,000 cases + 28,000 controls) and UC dataset (17,000 cases + 33,500 controls) to date. We conducted a meta-analysis of 5 CD cohorts of European ancestry using 3 pathway-based approaches and further performed replication studies in an independent cohort genotyped on the Immunochip and in another pediatric cohort of European ancestry. Similar meta-analysis was performed for UC cohorts. In addition to the multiple immune-related pathways that have been implicated in the genetic etiology of inflammatory bowel diseases before, we found significant associations involving genes in growth factor signaling for CD. This result was replicated in 2 independent cohorts of European ancestry. This association with growth factor activity is not unique to CD. We found a similar significant association with UC cohorts.
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Our findings suggest that genes involved in pathways of growth factor signaling may make joint contributions to the etiology of CD and UC, providing novel insight into the genetic mechanisms of these diseases. Final Decision: yes