{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:57:05Z","timestamp":1785243425271,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022QH365"],"award-info":[{"award-number":["ZR2022QH365"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021MH028"],"award-info":[{"award-number":["ZR2021MH028"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Aging\u2010related immunosenescence increases the risk of ulcerative colitis (UC), and investigating aging\u2010related causal genes in UC patients may aid in deciphering the molecular pathophysiology of UC. This study aims to identify aging\u2010related causal genes and explore their diagnostic value and underlying mechanisms in UC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and materials<\/jats:title><jats:p>Colonic transcriptome data, aging\u2010related genes, genome\u2010wide association studies (GWAS) data, and cis\u2010expression quantitative trait loci (cis\u2010eQTL) data were collected from databases. Aging\u2010related differentially expressed genes (ARDEGs) were identified, and functional enrichment analysis was performed. Summary\u2010data\u2010based Mendelian randomization (SMR) analysis and validation were performed to identify putative aging\u2010related causal genes (PARCGs). The expression levels and diagnostic efficacies of the PARCGs were evaluated and validated. Their correlations with immune infiltration were explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>371 ARDEGs were identified that were mainly involved in biological functions related to immunity, inflammation, and senescence. Through SMR, five genes (IRF1, CTSB, IL24, ME2, ERBB2) were first selected as latent aging\u2010related causal genes (LARCGs), and their expression levels were causally correlated with the risk of UC (IRF1, OR: 3.23, 95% CI: 1.80\u20135.77; CTSB, OR: 1.30, 95% CI: 1.14\u20131.47; IL24, OR: 1.66, 95% CI: 1.24\u20132.22; ME2, OR: 0.75, 95% CI: 0.63\u20130.89; ERBB2, OR: 0.21, 95% CI: 0.10\u20130.45). By replicating SMR analysis using the two additional UC GWAS data, three PARCGs (IRF1, ME2, ERBB2) were further determined. IRF1 was upregulated, while ME2 and ERBB2 were downregulated in UC, and all three PARCGs showed diagnostic potential for UC. Furthermore, correlation analysis revealed multiple correlations between the PARCGs and immune cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified three aging\u2010related genes (IRF1, ME2, ERBB2) through SMR for the first time that are causally correlated to the risk of UC. Further analysis revealed their diagnostic potential and explored their correlation with immune infiltration in UC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ahg.12600","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T08:59:17Z","timestamp":1746176357000},"page":"415-424","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mendelian Randomization Identifies Putative Aging\u2010Related Causal Genes With Diagnostic Potential in Ulcerative Colitis"],"prefix":"10.1111","volume":"89","author":[{"given":"Qi","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"},{"name":"Department of Gastroenterology, Cheeloo College of Medicine Shandong Provincial Hospital, Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangfei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"},{"name":"Department of Cardiac Surgery, Cheeloo College of Medicine Shandong Provincial Hospital, Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"},{"name":"Department of Gastroenterology, Cheeloo College of Medicine Shandong Provincial Hospital, Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"},{"name":"Department of Gastroenterology, Cheeloo College of Medicine Shandong Provincial Hospital, Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"},{"name":"Department of Gastroenterology, Cheeloo College of Medicine Shandong Provincial Hospital, Shandong University  Jinan Shandong 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