{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T05:24:32Z","timestamp":1764653072071,"version":"3.46.0"},"reference-count":54,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["22173065"],"award-info":[{"award-number":["22173065"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004829","name":"Science & Technology Department of Sichuan Province","doi-asserted-by":"crossref","award":["2024NSFSC1298"],"award-info":[{"award-number":["2024NSFSC1298"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007433","name":"China West Normal University","doi-asserted-by":"publisher","award":["23KE022"],"award-info":[{"award-number":["23KE022"]}],"id":[{"id":"10.13039\/501100007433","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Charles Bronfman Institute for Personalized Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Ulcerative colitis (UC) is a major form of inflammatory bowel disease affecting the gastrointestinal tract. Increasing evidence suggests UC is predisposed to co-occurring with other autoimmune diseases, yet its pathogenesis remains insufficiently understood. Large-scale biobank-based cross-trait genetic analyses may provide insights into the origins of UC and its comorbidities. Methods: Using the UK Biobank and Mount Sinai BioMe Biobank, we conducted genome-wide association studies (GWASs) in individuals of European ancestry. High-impact rare variants were aggregated for collapsing analysis. Genome-wide significant variants were tested in a phenome-wide association study (PheWAS) to explore UC comorbidities. Polygenic risk scores (PRSs) were derived from large-scale GWASs under different thresholds and functionalities, and the best-performing PRS was further applied in a PRS-based PheWAS. Genetic correlation between UC and highly associated traits was evaluated. Results: GWASs identified four genome-wide significant loci, including two novel variants (rs2314757, p = 4.82 \u00d7 10\u221211, OR = 0.81; rs6869382, p = 2.48 \u00d7 10\u22128, OR = 0.83) and two previously reported UC-associated sites (rs4654925, p = 1.85 \u00d7 10\u22128, OR = 0.84; rs2836882, p = 1.23 \u00d7 10\u221211, OR = 0.78) outside the HLA region. The optimal PRS, constructed with SNPs at p &lt; 0.05, conferred an odds ratio of 5.86 (95% CI: 5.05\u20136.86) for UC in individuals with the highest versus lowest quintile. Both variant- and PRS-based PheWASs consistently highlighted type 1 diabetes (T1D) as the most significant comorbidity, confirmed by genetic correlation analysis. Conclusions: This study reveals novel loci contributing to UC and highlights comorbidities with shared genetic bases. UC PRSs demonstrated strong utility beyond risk prediction, effectively identifying UC-associated traits. A robust genetic correlation was established between UC and T1D.<\/jats:p>","DOI":"10.3390\/genes16121431","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T09:34:37Z","timestamp":1764581677000},"page":"1431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling Novel Traits Associated with Ulcerative Colitis via Phenome-Wide Associations Enhanced by Polygenic Risk Statistics"],"prefix":"10.3390","volume":"16","author":[{"given":"Yiming","family":"Wu","sequence":"first","affiliation":[{"name":"College of Life Science, China West Normal University, Nanchong 637009, China"},{"name":"Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong 637009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Chemistry, Sichuan University, Chengdu 610065, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meltem Ece","family":"Kars","sequence":"additional","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Science, China West Normal University, Nanchong 637009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7365-0344","authenticated-orcid":false,"given":"Menglong","family":"Li","sequence":"additional","affiliation":[{"name":"College of Chemistry, Sichuan University, Chengdu 610065, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuval","family":"Itan","sequence":"additional","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41572-020-0205-x","article-title":"Ulcerative colitis","volume":"6","author":"Kobayashi","year":"2020","journal-title":"Nat. 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