{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T13:21:24Z","timestamp":1788009684261,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Herpes simplex viruses (HSV) have been detected within the synovial joint cavity, a secluded area of inflammation that may harbor etiological agents. However, the role of HSV\u20101\/2 infection in arthritis pathogenesis remains ambiguous. In this study, we integrate cross\u2010sectional epidemiology and genetic associations to elucidate their relationships and uncover causal mechanisms. We analyzed cross\u2010sectional data from 18,292 NHANES participants (1999\u20132016) using multivariable\u2010adjusted logistic regression to assess associations between anti\u2010HSV\u20101\/2 IgG seropositivity and arthritis\u2010related risks. Complementary analyses included linkage disequilibrium score regression (LDSC) and bidirectional Mendelian randomization (MR) using genetic instruments for anti\u2010HSV IgG levels to explore genetic correlations and infer causality. Initial observational findings demonstrated significant positive associations between HSV\u20101\/2 IgG seropositivity and arthritis risk (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001); however, these associations lost significance after multivariable adjustment. Notably, after multivariable adjustment, subtype analyses revealed that HSV\u20102 IgG seropositivity was linked to increased risks of rheumatoid arthritis (RA) (OR: 1.40, 95% CI: 1.04\u20131.88) and osteoarthritis (OA) (OR: 1.39, 95% CI: 1.07\u20131.81), while HSV\u20101 IgG seropositivity correlated with an unknown\u2010arthritis subtype (OR: 1.38, 95% CI: 1.08\u20131.75). Moreover, MR analyses uncovered divergent causal effects: anti\u2010HSV\u20101 IgG levels were protective against OA (OR: 0.90, 95% CI: 0.82\u20130.98), whereas anti\u2010HSV\u20102 IgG levels modestly increased OA risk (OR: 1.05, 95% CI: 1.01\u20131.09). No reverse causation or genetic correlation was observed. This study's innovative integration of epidemiological and genetic methodologies not only clarifies the distinct roles of HSV sub\u2010types in arthritis but also identifies HSV\u20102 as a potential causal factor in OA, thereby opening new avenues for therapeutic targeting.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/gepi.70020","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T12:45:36Z","timestamp":1761223536000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Associations of Herpes Simplex Virus Type 1\/2 IgG Seropositivity and Arthritis Subtypes: Integrating Cross\u2010Sectional Epidemiology and Genetic Association Analyses"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8013-8532","authenticated-orcid":false,"given":"Haining","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The First People's Hospital of Lianyungang The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First Affiliated Hospital of Kangda College of Nanjing Medical University Lianyungang Jiangsu Province China"},{"name":"Kangda College of Nanjing Medical University Lianyungang Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Shen","sequence":"additional","affiliation":[{"name":"Jiwei Prison Hospital of Shandong Jinan Shandong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1972-5410","authenticated-orcid":false,"given":"Changzhou","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First People's Hospital of Lianyungang The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First Affiliated Hospital of Kangda College of Nanjing Medical University Lianyungang Jiangsu Province 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