{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T20:22:39Z","timestamp":1787602959747,"version":"build-2736575974"},"reference-count":69,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"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":["Brain and Behavior"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The \u201cgut\u2013brain axis\u201d provides a theoretical foundation for the connection between intestinal and neurological diseases, but whether this reflects a shared genetic etiology or causal relationships exist remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used genome\u2010wide association study summary data from FinnGen and UK Biobank to investigate the genetic correlations and causal relationships between three intestinal diseases and six neurological diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We observed positive global genetic correlations between irritable bowel syndrome and epilepsy (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>g\u00a0<\/jats:sub>\n                      =\u00a00.429,\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a01.53\u00a0\u00d7\u00a010\n                      <jats:sup>\u22122<\/jats:sup>\n                      ), and stroke (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>g\u00a0<\/jats:sub>\n                      =\u00a00.368,\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a02.56\u00d710\n                      <jats:sup>\u22122<\/jats:sup>\n                      ). Upon dividing the whole genome into 1703 independent regions, local genetic correlations were identified in a region between ulcerative colitis and multiple sclerosis (Chr6: 31571218\u201332682664). We also identified 12 novel pleiotropic SNPs shared between intestinal and neurological diseases, as well as a functional gene shared between ulcerative colitis and multiple sclerosis. SNP heritability enrichment analysis indicated that ulcerative colitis and multiple sclerosis have enrichment in several immune cells. Two\u2010sample Mendelian randomization indicated the causal effect of Crohn's disease on Parkinson's disease (FDR\u00a0=\u00a01.34\u00a0\u00d7\u00a010\n                      <jats:sup>\u22122<\/jats:sup>\n                      , OR\u00a0=\u00a01.092). The methylome Mendelian randomization analysis also showed causal relationships between several intestinal and neurological diseases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Through comprehensive and systematic statistical analysis, we identified the global and local genetic correlations and causal relationships between several intestinal and neurological diseases and discovered shared pleiotropic loci and genes between them. Furthermore, the consistent SNP heritability enrichment observed in immune cells also indicated the crucial role of the immune system in the \u201cgut\u2013brain axis.\u201d<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71269","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T06:29:06Z","timestamp":1771309746000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling Shared Genetic Architectures and Causality: Intestinal Diseases and Neurological Diseases"],"prefix":"10.1002","volume":"16","author":[{"given":"Ning","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Epidemiology, School of Public Health Harbin Medical University  Harbin P.R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1845-9285","authenticated-orcid":false,"given":"Zhuobo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology The Fourth Affiliated Hospital of Harbin Medical University  Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9869-9504","authenticated-orcid":false,"given":"Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health Harbin Medical University  Harbin P.R. China"},{"name":"NHC Key Laboratory of Etiology and Epidemiology (23618504) Harbin Medical University  Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7425-5773","authenticated-orcid":false,"given":"Yashuang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health Harbin Medical University  Harbin P.R. China"},{"name":"NHC Key Laboratory of Etiology and Epidemiology (23618504) Harbin Medical University  Harbin P.R. 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C. C.White D. A.Bennett H. U.Klein andP. L.De Jager.2023. \u201cGenetic Insights Into the Association Between Inflammatory Bowel Disease and Alzheimer's Disease.\u201dmedRxiv.https:\/\/doi.org\/10.1101\/2023.04.17.23286845.","DOI":"10.1101\/2023.04.17.23286845"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1097\/cm9.0000000000000748"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.11.011"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3538"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2387800"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.71269","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/brb3.71269","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.71269","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T19:45:56Z","timestamp":1787600756000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.71269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":69,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/brb3.71269"],"URL":"https:\/\/doi.org\/10.1002\/brb3.71269","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/BRB3.71269\/v1\/decision1","asserted-by":"object"}]},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"value":"2162-3279","type":"print"},{"value":"2162-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71269"}}