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This investigation aims to examine the causal association between viral infections of the central nervous system (VICNS) and inflammatory diseases of the central nervous system (IDCNS) and knee osteoarthritis (KOA) at the genetic level.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In this investigation, VICNS and IDCNS were considered as primary exposure variables, while KOA served as the primary outcome. Employing a two-sample mendelian randomization (MR) approach, we conducted an analysis utilizing summary data derived from genome-wide association studies (GWAS). The GWAS summary data pertaining to VICNS and IDCNS were procured from the Finnish consortium, whereas the IEU OpenGWAS database furnished the requisite data for KOA. To ensure the robustness of our genetic causal assessment, a comprehensive array of sensitivity analyses was undertaken, encompassing evaluations of heterogeneity, horizontal pleiotropy, outlier identification, leave-one-out analyses, and assessment of the normal distribution.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The results of the MR analyses revealed a suggestive positive genetic causal relationship between VICNS and KOA (<jats:italic>P<\/jats:italic>\u2009=\u20090.012, odds ratio [OR] with a 95% confidence interval [CI] of 1.033 [1.007\u20131.059]). Conversely, the MR analyses did not indicate any evidence of genetic causation between IDCNS and KOA (<jats:italic>P<\/jats:italic>\u2009=\u20090.575, OR 95% CI\u2009=\u20090.986 [0.940\u20131.035]). Importantly, the genetic causal assessment of the exposure and outcome variables did not demonstrate any indications of heterogeneity, horizontal pleiotropy, or outliers. Furthermore, this assessment remained robust against the influence of individual single nucleotide polymorphisms (SNPs) and exhibited adherence to a normal distribution.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The result of this study has elucidated a suggestive positive genetic causal link between the VICNS and KOA. However, no such genetic causal relationship was observed between the IDCNS and KOA. These findings substantiate the genetic underpinnings supporting the association between the CNS and OA.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s40520-025-02927-7","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T04:03:40Z","timestamp":1737432220000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Viral infections of the central nervous system increase the risk of knee osteoarthritis: a two-sample mendelian randomization study"],"prefix":"10.1007","volume":"37","author":[{"given":"Mingyi","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yani","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengfei","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiale","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianjie","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wensen","family":"Jing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"issue":"3","key":"2927_CR1","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.cger.2010.03.001","volume":"26","author":"Y Zhang","year":"2010","unstructured":"Zhang Y, Jordan JM (2010) Epidemiology of Osteoarthritis. 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