{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:16:06Z","timestamp":1788311766816,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Population\u2010based evidence directly linking liver diseases to brain disorders is limited, and its genetic and biochemical associations remain unclear. Our aim is to examine the links between liver diseases and brain disorders. This prospective cohort study utilized data from 492\u2009059 participants in the UK Biobank. We identified 508 cases of alcoholic liver disease (ALD), 583 cases of non\u2010alcoholic fatty liver disease (NAFLD), and 557 cases of viral hepatitis (VH) based on International Classification of Diseases (ICD) codes. Initially, we employed multiple linear and logistic regression to assess associations between liver diseases, polygenic risk score (PRS), inflammatory and metabolic biomarkers, and brain function. Cox proportional hazard models were then applied to determine the impact of liver diseases on the incidence of brain disorders. Ultimately, structural equation models were used to explore potential genetic and biomarker pathways. During a median follow\u2010up of 14.46\u2009years, participants with ALD, NAFLD, and VH demonstrated poorer cognition, mental health, and motor function compared to the healthy group, with\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05 for false discovery rate (FDR\u2010Q\u2009&lt;\u20090.05). They exhibited increased risks for dementia (hazard ratios [HRs]: 2.28\u20134.10; FDR\u2010Q\u2009&lt;\u20090.001), major depressive disorder (HRs: 2.25\u20133.23; FDR\u2010Q\u2009&lt;\u20090.001), and generalized anxiety disorder (HRs: 1.70\u20132.66; FDR\u2010Q\u2009&lt;\u20090.01). Additionally, C\u2010reactive protein, neutrophil\u2010to\u2010lymphocyte ratio, platelets, and low\u2010density lipoprotein lipid components mediated the associations between PRS, liver diseases, and brain disorders. Our findings demonstrated that liver diseases were risk factors for brain disorders, with genetic and biochemical associations contributing to these risks.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70066-fig-0008-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70066","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T01:44:06Z","timestamp":1744681446000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Liver Diseases and Brain Disorders: Genetic Mechanisms and Biomarker Pathways in a Prospective Cohort Study From the\n                    <scp>UK<\/scp>\n                    Biobank"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9383-4361","authenticated-orcid":false,"given":"Hai\u2010Hua","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7559-1215","authenticated-orcid":false,"given":"Pei\u2010Yang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology &amp; Innovation Center for Neurological Disorders, National Center for Neurological Disorders, Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology for Brain\u2010Inspired Intelligence Fudan University  Shanghai China"},{"name":"Key Laboratory of Computational Neuroscience and Brain\u2010Inspired Intelligence, Ministry of Education Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao\u2010Chen","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang\u2010Ling","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao\u2010Lin","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital Qingdao University  Qingdao China"},{"name":"Department of Neurology, Qingdao Hospital University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital)  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8759-7588","authenticated-orcid":false,"given":"Lan","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital Qingdao University  Qingdao China"},{"name":"Department of Neurology, Qingdao Hospital University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital)  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0494-2241","authenticated-orcid":false,"given":"Hui\u2010Fu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital Qingdao University  Qingdao China"},{"name":"Department of Neurology, Qingdao Hospital University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital)  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100031\u20101276643"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.01.037"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003853"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.99"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102424"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010023\u201002559\u2010z"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1017\/S204579602000116X"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13346"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.12.012"},{"key":"e_1_2_11_11_1","unstructured":"Denaxas S. 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