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We obtained data on mental disorder-related gene methylation, expression, protein levels, and summary statistics of IBD, and performed Summary data-based Mendelian randomization and colocalization analyses to explore the causal associations and shared causal genetic variants between multiple molecular traits and IBD. Integrating multi-omics data, we found\n                    <jats:italic>QDPR<\/jats:italic>\n                    ,\n                    <jats:italic>DBI and MAX<\/jats:italic>\n                    are associated with ulcerative colitis (UC) risk, while\n                    <jats:italic>HP<\/jats:italic>\n                    is linked to IBD risk. Inverse associations between gene methylation (cg0880851 and cg26689483) and expression are observed in\n                    <jats:italic>QDPR<\/jats:italic>\n                    , consistent with their detrimental role in UC. Methylation of\n                    <jats:italic>DBI<\/jats:italic>\n                    (cg11066750) protects against UC by enhancing expression. Higher levels of\n                    <jats:italic>DBI<\/jats:italic>\n                    (OR\u2009=\u20090.79, 95%CI\u2009=\u20090.69\u20130.90) and\n                    <jats:italic>MAX<\/jats:italic>\n                    (OR\u2009=\u20090.74, 95%CI\u2009=\u20090.62\u20130.90) encoded proteins are inversely associated with UC risk, while higher\n                    <jats:italic>QDPR<\/jats:italic>\n                    (OR\u2009=\u20091.17, 95%CI\u2009=\u20091.07\u20131.28) and\n                    <jats:italic>HP<\/jats:italic>\n                    (OR\u2009=\u20091.09, 95%CI\u2009=\u20091.04\u20131.14) levels increase UC and IBD risk. Our findings advance the understanding of IBD\u2019s pathogenic mechanisms and gut-brain interaction.\n                  <\/jats:p>","DOI":"10.1038\/s41398-025-03299-2","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T02:53:44Z","timestamp":1742525624000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multi-omics insight into the molecular networks of mental disorder related genetic pathways in the pathogenesis of inflammatory bowel disease"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2950-8548","authenticated-orcid":false,"given":"Meng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haosen","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqian","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0046-6663","authenticated-orcid":false,"given":"Jing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6880-2577","authenticated-orcid":false,"given":"Xue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"3299_CR1","first-page":"27","volume":"58","author":"O Fabi\u00e1n","year":"2022","unstructured":"Fabi\u00e1n O, Kamaradov\u00e1 K. 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