{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:05:46Z","timestamp":1790139946870,"version":"4.0.1"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic pathways are crucial in hepatocellular carcinoma (HCC) pathogenesis, but causal metabolic genes remain unclear. This study used Summary data\u2010based Mendelian Randomization (SMR) and colocalization to identify metabolism\u2010related genetic loci influencing HCC risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Differentially expressed genes in hepatic malignancy phenotype versus normal tissues from TCGA and GTEx were analyzed. Metabolism\u2010related candidates were examined via SMR and colocalization using multi\u2010omics data: methylation (mQTL), expression (eQTL), and protein (pQTL) quantitative trait loci.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Multi\u2010omics integration identified NIT2 as a key metabolic regulator for HCC. The cg13016775 locus of NIT2 was associated with elevated HCC risk at gene (OR\u2009=\u20091.618, 95% CI: 1.199\u20132.182) and protein (OR\u2009=\u20094.432, 95% CI: 1.783\u201311.018) levels. Colocalization supported a shared causal variant (PPH4\u2009&gt;\u20090.6), linking NIT2 to hepatocarcinogenesis via metabolic regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides multi\u2010omics evidence for NIT2 as a potential causal gene in HCC, enhancing understanding of metabolic contributions to HCC pathogenesis and highlighting integrative genomics for uncovering causal relationships.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jgm.70111","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:39:30Z","timestamp":1788327570000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Multi\u2010Omics Mendelian Randomization Analysis Identifies NIT2 as a Potential Metabolic Risk Gene in Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9565-8803","authenticated-orcid":false,"given":"Ziyue","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1222-6491","authenticated-orcid":false,"given":"Qinghua","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical University  Chongqing 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