P4278 - Unraveling the Genetic Overlap Between Autism, Inflammatory Bowel Diseases, and Celiac Disease: A Bioinformatics Approach

Mohammed Al-Zakwani, MD, MS¹, Mahdi Malekpour, MD², Mohamad Parhizkar, MD², Fahimeh Golabi, MD², Rachel Thompson, MD³, Saeed Soleymanjahi, MD³, Elnaz Chohedri, MD^2
1Yale New Haven Hospital, New Haven, CT; ²Shiraz University of Medical Sciences, Shiraz, Fars, Iran; ³Yale New Haven Health, New Haven, CT

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social interactions, communication, and repetitive behaviors. There is a significant occurrence of gastrointestinal issues associated with ASD, including Celiac disease and Inflammatory Bowel Disease (IBD). Therefore, it has been suggested that patients should be screened for IBD. This study aims to use bioinformatics tools to identify shared genetic mutations between ASD, IBD, and Celiac disease.

Methods: Databases including DisGeNET, the Genome Wide Association Study (GWAS) Catalog, and Ensembl were queried to pinpoint variation disease associations (VDAs) for Autism, Celiac disease, and IBD. The Molbiotools software was used to discover shared VDAs, which were then validated through a review of original articles and resources from the databases. These original articles were also reviewed to understand the possible shared pathogenesis between these diseases based on common genetic mutations.

Results: Through this search, 2367 unique VDAs were identified for ASD, 458 for Celiac disease, and 1912 for IBD. However, only two shared VDAs among Autism, Celiac disease, and IBD were validated. These shared VDAs were located in Methylenetetrahydrofolate reductase (MTHFR) and Myosin IXB (MYO9B). In particular, the T allele of rs181133 in MTHFR and the G allele of rs1545620 in MYO9B were associated with all three diseases.

Discussion: This study indicates that mutations in MYO9B and MTHFR could simultaneously contribute to the pathogenesis of ASD, IBD, and Celiac disease by affecting both brain and intestinal cells. This discovery could lead to the development of targeted therapies and screenings to mitigate the impact of these mutations. Furthermore, these shared genetic factors could characterize the potential shared pathogenesis between ASD, IBD, and Celiac disease. This study opens possibilities for further clinical validation which could inform future screening and treatment strategies.



Disclosures:


Mohammed Al-Zakwani, MD, MS¹, Mahdi Malekpour, MD², Mohamad Parhizkar, MD², Fahimeh Golabi, MD², Rachel Thompson, MD³, Saeed Soleymanjahi, MD³, Elnaz Chohedri, MD². P4278 - Unraveling the Genetic Overlap Between Autism, Inflammatory Bowel Diseases, and Celiac Disease: A Bioinformatics Approach, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.