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Two\u2010step mediation MR analysis was further performed to explore indirect factors that may influence the relationship between SLE and JME. Summary data on SADs were extracted from the Integrative Epidemiology Unit Open genome\u2010wide association study database, and summary statistics for JME were acquired from the International League Against Epilepsy Consortium. The inverse\u2010variance weighted (IVW) method was used for primary analysis, supplemented by MR\u2010Egger and weighted median. In the univariable MR analysis, IVW results indicated a causal relationship between SLE and an increased risk of JME (odds ratio\u2009=\u20091.0030, 95% confidence interval, 1.0004\u20131.0057; <jats:italic>p<\/jats:italic>\u2009=\u20090.023). The subsequent mediation MR analysis showed that inflammatory cytokines may not be the mediating factors between SLE and JME, while the inverse MR analysis found no significant relationship. Our study indicated that genetic susceptibility to SLE was causally linked to JME. However, subsequent mediation analysis failed to identify the potential mediators that could influence this relationship. Moreover, evidence suggested that other SADs were not causally associated with JME. This study may provide guidance for screening risk factors for seizures and exploring potential treatments in SLE and JME, and even all SADs and JME.<\/jats:p>","DOI":"10.1002\/ibra.12191","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T12:50:22Z","timestamp":1736254222000},"page":"98-105","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The causal relationship between systemic lupus erythematosus and juvenile myoclonic epilepsy: A Mendelian randomization study and mediation analysis"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0860-2495","authenticated-orcid":false,"given":"Sirui","family":"Chen","sequence":"first","affiliation":[{"name":"The Second Hospital &amp; Clinical Medical School Lanzhou University Lanzhou 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