{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:38:00Z","timestamp":1790959080568,"version":"4.1.0"},"reference-count":90,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zuckerman STEM leadership program and Israel Science Foundation","award":["1994\/21"],"award-info":[{"award-number":["1994\/21"]}]},{"name":"Zuckerman STEM leadership program and Israel Science Foundation","award":["3252\/21"],"award-info":[{"award-number":["3252\/21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Inflammatory bowel disease (IBD), comprising Crohn\u2019s disease (CD) and ulcerative colitis (UC), arises from complex genetic and environmental interactions. Here, we integrate genome-wide association study (GWAS) meta-analyses with tissue-specific expression data from GTEx to map the polygenic architecture of IBD and its systemic implications. We identified 69 genome-wide significant single-nucleotide polymorphisms (SNPs) across 26 genes shared by CD and UC, revealing an almost equal partition of subtype-specific (50.7%) and shared (49.3%) risk variants. IL23R exhibited the highest allelic heterogeneity\u2014three UC-specific, one CD-specific, and three shared SNPs\u2014while ATG16L1\u2032s four CD-specific variants underscored autophagy\u2019s pivotal role in CD. Chromosomal mapping revealed distinct regulatory hotspots: UC-only loci on chromosomes 1 and 6, CD-only loci on chromosomes 10 and 16, and shared loci on chromosomes 7 and 19. Pathway enrichment emphasized IL-23\/IL-17, Th17 differentiation, NF-\u03baB, and JAK\u2013STAT signaling as central to IBD pathogenesis. GTEx analyses showed uniformly high expression of IBD genes in gastrointestinal tissues, but pronounced heterogeneity across brain regions, including the cerebellum, frontal cortex, and hippocampus. This neuro-expression, together with enrichment of neurotrophin and neurodegeneration pathways and a nearly two-fold gene overlap with autism spectrum disorder, schizophrenia, and depression (FDR &lt; 0.05), provides integrative evidence for gut\u2013brain axis involvement in IBD. These findings consolidate prior work while extending perspectives on systemic disease implications. This study consolidates and systematizes dispersed genetic and transcriptomic findings into a unified reference framework. Our results highlight recurrent immune-regulatory and neuro-inflammatory pathways shared between gut and brain, offering a resource to guide future mechanistic, clinical, and translational investigations in IBD and related disorders.<\/jats:p>","DOI":"10.3390\/biology14101433","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T14:29:17Z","timestamp":1760711357000},"page":"1433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["From Genome-Wide SNPs to Neuroimmune Crosstalk: Mapping the Genetic Landscape of IBD and Its Brain Overlap"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9503-3793","authenticated-orcid":false,"given":"Utkarsh","family":"Tripathi","sequence":"first","affiliation":[{"name":"Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yam","family":"Stern","sequence":"additional","affiliation":[{"name":"Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inbal","family":"Dagan","sequence":"additional","affiliation":[{"name":"Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Nayak","sequence":"additional","affiliation":[{"name":"Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0059-1977","authenticated-orcid":false,"given":"Eva","family":"Romanovsky","sequence":"additional","affiliation":[{"name":"Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eran","family":"Zittan","sequence":"additional","affiliation":[{"name":"The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3525433, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2644-7068","authenticated-orcid":false,"given":"Shani","family":"Stern","sequence":"additional","affiliation":[{"name":"Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1038\/ng.717","article-title":"Genome-Wide Meta-Analysis Increases to 71 the Number of Confirmed Crohn\u2019s Disease Susceptibility Loci","volume":"42","author":"Franke","year":"2010","journal-title":"Nat. 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