{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T20:15:48Z","timestamp":1783196148295,"version":"3.54.6"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62222104"],"award-info":[{"award-number":["62222104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62172130"],"award-info":[{"award-number":["62172130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010009","name":"Heilongjiang Provincial Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["LBH\u2010Q20030"],"award-info":[{"award-number":["LBH\u2010Q20030"]}],"id":[{"id":"10.13039\/501100010009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Inflammatory bowel disease (IBD) with the two predominant endophenotypes\u2014Crohn's disease (CD) and ulcerative colitis (UC)\u2014represents a group of chronic gastrointestinal inflammatory conditions. Since most genetic associations with IBD are often limited to independent subtypes, we reported a genome\u2010wide association study (GWAS) cross\u2010trait analysis combined with CD and UC to enhance statistical power. Initially, we detected 256 association signals at 54 genomic susceptibility loci and further characterized the functionality of variants within these regions. Subsequently, we revealed tissue and cell\u2010specific heritability enrichment, particularly in whole blood, small intestine terminal ileum, spleen, lung, and colon transverse. Leveraging multi\u2010omics datasets, we adopted a two\u2010pronged approach comprising summary data\u2010based Mendelian randomization (SMR) and transcriptome\u2010wide association study (TWAS) to pinpoint likely causal genes and variants. Further, RNA\u2010seq analysis facilitated the evaluation of differential expression and co\u2010expression in intestinal tissues. Through a multi\u2010stage prioritization strategy, compelling evidence for putative targets was nominated; notably highlighting several potential susceptibility genes such as\n                    <jats:italic>IL27<\/jats:italic>\n                    and\n                    <jats:italic>SBNO2<\/jats:italic>\n                    . Finally, we utilized Mendelian randomization (MR) analysis with diverse datasets to verify the convergence of these two endophenotype\u2010driven genes. Our investigation yields valuable insights to inform genetic mechanisms in IBD and reveal potential causal gene targets.\n                  <\/jats:p>","DOI":"10.1096\/fj.202402489r","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T10:25:36Z","timestamp":1736504736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Joint analysis of genome\u2010wide cross\u2010trait and multi\u2010omics reveals molecular mechanisms of inflammatory bowel disease and nominates its novel therapeutic genes"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6488-2707","authenticated-orcid":false,"given":"Zijun","family":"Zhu","sequence":"first","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5854-5806","authenticated-orcid":false,"given":"Rongxing","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5271-3858","authenticated-orcid":false,"given":"Hailong","family":"Li","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2226-2073","authenticated-orcid":false,"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2982-6070","authenticated-orcid":false,"given":"Guanzhi","family":"He","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7339-2574","authenticated-orcid":false,"given":"Meiyu","family":"Du","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6249-2279","authenticated-orcid":false,"given":"Senwei","family":"Tan","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6665-6710","authenticated-orcid":false,"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin Heilongjiang China"},{"name":"NHC Key Laboratory of Molecular Probe and Targeted Diagnosis and Therapy Harbin Medical University  Harbin Heilongjiang China"},{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.5217\/ir.2018.16.1.26"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu174"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25768-0"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-017-0009-4"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-323868"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3359"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.734"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01261-5"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004219"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2021.27"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac966"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01365-3"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.149.1.113"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02560-3"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3538"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3506"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-326451"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1055"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1147"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyg070"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0175-2"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20079-2"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-00287-2"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.15555.1"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007081"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202303349"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.03.016"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312135"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01428-5"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000818"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izad153"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022018494"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21651"},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21998"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202402489R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:37:41Z","timestamp":1761676661000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202402489R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,10]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,15]]}},"alternative-id":["10.1096\/fj.202402489R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202402489r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,10]]},"assertion":[{"value":"2024-10-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70305"}}