{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:08:57Z","timestamp":1778742537132,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"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":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Introduction<\/jats:bold>\n                    : Some observational studies indicated that AQP4\u2010ab\u2010positive neuromyelitis optica spectrum disorder (NMOSD) may predispose to hydrocephalus. However, the causal relationship between NMOSD and hydrocephalus remains elusive. We used bidirectional Mendelian randomization (MR) to examine the causal effect of AQP4\u2010ab\u2010positive NMOSD and hydrocephalus.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    : The exposure GWAS data used in this study were obtained from the GWAS Catalog, which included 132 AQP4\u2010ab\u2010positive patients and 1244 normal controls. The outcome GWAS data for hydrocephalus (\n                    <jats:italic>N<\/jats:italic>\n                    _\n                    <jats:sub>case<\/jats:sub>\n                    \u00a0=\u00a02455,\n                    <jats:italic>N<\/jats:italic>\n                    _\n                    <jats:sub>control<\/jats:sub>\n                    \u00a0=\u00a0382,198) were obtained from FinnGen R10. We used the inverse\u2010variance weighted (IVW) method to perform the principal analyses. Then, we used the Cochrane\n                    <jats:italic>Q<\/jats:italic>\n                    \u2010statistics test to assess the presence of heterogeneity and MR\u2010Egger\u2011intercept test to evaluate the pleiotropy for sensitivity analyses. A reverse MR analysis was used to investigate the potential for reverse causation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : In the IVW analysis, we found that genetically predicted AQP4\u2010ab\u2010positive NMOSD was significantly associated with the increasing risk of hydrocephalus (OR\u00a0=\u00a01.05\n                    <jats:styled-content>;<\/jats:styled-content>\n                    95% CI: 1.02\u20131.08;\n                    <jats:italic>p\u00a0<\/jats:italic>\n                    =\u00a07.65\u00a0\u00d7\u00a010\n                    <jats:sup>\u22125<\/jats:sup>\n                    ). In reverse MR analysis, we did not find genetically predicted hydrocephalus significantly associated with AQP4\u2010ab\u2010positive NMOSD (\n                    <jats:italic>p\u00a0<\/jats:italic>\n                    &gt;\u00a00.05). In the sensitivity analysis, both the primary and reverse MR results exhibit no heterogeneity and horizontal pleiotropy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Discussion<\/jats:bold>\n                    : Our results indicate that genetically predicted AQP4\u2010ab\u2010positive NMOSD significantly increases the risk of hydrocephalus. The reduced immune activity of AQP4 may play an important role in the pathogenesis of hydrocephalus.\n                  <\/jats:p>","DOI":"10.1002\/brb3.70804","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T05:05:46Z","timestamp":1760591146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AQP4\u2010ab\u2010Positive Neuromyelitis Optica Spectrum Disorder Increases the Risk of Hydrocephalus: A Bidirectional Mendelian Randomization Study"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4085-8186","authenticated-orcid":false,"given":"Weitao","family":"Zhong","sequence":"first","affiliation":[{"name":"Neurosurgery Center, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Southern Medical University  Guangzhou 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Neurosurgery Center, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wangming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Neurosurgery Center, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Southern Medical University  Guangzhou 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