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The primary analysis employed five Mendelian randomization methods to evaluate causal effects, while linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) were utilized to investigate genetic correlations. Additionally, significant pleiotropic SNPs were identified using pleiotropic analysis under the composite null hypothesis (PLACO) and functional mapping and annotation (FUMA). Finally, enrichment analysis was conducted to explore the biological pathways associated with the identified pleiotropic genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MR analysis revealed a significant causal relationship between AD and an enhanced risk of constipation was demonstrated (OR = 1.043, 95% CI: 1.015\u20131.073, p\u2009=\u20090.003), while no causality was found between PD, MS, ALS, LBD, and the risk of constipation (p\u2009&gt;\u20090.05). LDSC and HDL analysis revealed a significant positive genetic correlation between AD and constipation. Using PLACO combined with FUMA, we identified 30 overlapping pleiotropic loci, with pathway enrichment analysis revealing important biological pathways related to A\u03b2 metabolism and processing, tau protein process, and the complement and coagulation cascades.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study indicates that AD is a contributing factor to constipation and uncovers the complex genetic mechanisms linking AD and constipation, which holds significant implications for diagnosis and treatment of both conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/25424823251362469","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T06:21:18Z","timestamp":1753338078000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Causal associations and shared genetic etiology between neurodegenerative diseases and constipation"],"prefix":"10.1177","volume":"9","author":[{"given":"Weidong","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anlong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanman","family":"Chang","sequence":"additional","affiliation":[{"name":"Center for Clinical Research, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyi","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care 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