{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:46:56Z","timestamp":1787240816301,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"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":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study investigates the shared genetic basis between gastrointestinal (GI) diseases and neurodegenerative diseases (ND) using genome\u2010wide association study (GWAS) data and statistical genetic methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>GWAS data, primarily from European populations, covered four types of GI diseases and three types of ND. Genetic correlations were assessed using Linkage Disequilibrium Score Regression (LDSC), High\u2010Definition Likelihood (HDL), and Local Analysis of Covariant Annotation (LAVA). Pleiotropic and functional genetic overlaps were explored using the Genomic Partitioning Approach (GPA), pleiotropic analysis under the composite null hypothesis (PLACO), and Functional Mapping and Annotation of Genetic Associations (FUMA). Multi\u2010marker analysis of genomic annotation (MAGMA) was used for biological annotation and enrichment analysis, while summary data\u2010based Mendelian randomization (SMR) analysis linked pleiotropic genes with gene expression. Two\u2010sample Mendelian randomization (TSMR) investigated potential causal relationships.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Significant genetic correlations and shared genetic features were identified. The research identified 1,457 pleiotropic single nucleotide variants(SNVs) distributed across 47 chromosomal regions and 74pleiotropic genes, predominantly involved in pathways related tosignal transduction, amyloid regulation, and lipid metabolism. Nine colocalization loci (PPH4 &gt; 0.8) were identified, while SMR analysis linked 26 pleiotropic genes to disease expression levels. Key genes, including\n                      <jats:italic>EP300<\/jats:italic>\n                      ,\n                      <jats:italic>CHRNB1<\/jats:italic>\n                      ,\n                      <jats:italic>KNOP1<\/jats:italic>\n                      ,\n                      <jats:italic>P2RY14<\/jats:italic>\n                      , and\n                      <jats:italic>POLR2A<\/jats:italic>\n                      , were significantly associated with both disease types. Drug\u2010gene interaction analysis highlighted 8 genes with drug targets, among which\n                      <jats:italic>EP300<\/jats:italic>\n                      ,\n                      <jats:italic>PRKCB<\/jats:italic>\n                      ,\n                      <jats:italic>VKORC1<\/jats:italic>\n                      , and\n                      <jats:italic>CHRNB1<\/jats:italic>\n                      were found to anchor enriched pathways including purinergic signaling, amyloid\/protein aggregation, and cholesterol\/lipoprotein transport. Mendelian randomization corroborated possible causal association.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study confirms a shared genetic basis between GI and ND, emphasizing the gut\u2010brain axis in their etiology. These findings offer clues about shared pathways, potential therapeutic targets, and future research directions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71029","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T07:00:06Z","timestamp":1763967606000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive Genome\u2010Wide Analysis of Shared Genetic Factors in Gastrointestinal and Neurodegenerative Diseases"],"prefix":"10.1002","volume":"15","author":[{"given":"Yan","family":"Jiang","sequence":"first","affiliation":[{"name":"Laboratory Medicine Diagnostic Centre, The First Affiliated Hospital Xinjiang Medical University  Urumqi Xinjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department Laboratory, The Six Affiliated Hospital Xinjiang Medical 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