{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T01:13:41Z","timestamp":1777770821983,"version":"3.51.4"},"reference-count":56,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"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":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) is a complex autoimmune disease with unclear pathogenesis. Recent studies suggest that immune cell phenotypes may play a causal role. This study aimed to uncover causal immune cell types, key genes, and potential biomarkers using Mendelian randomization (MR) and machine learning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A two\u2010sample MR analysis was performed on 731 immune cell traits to assess their causal relationship with SLE risk. Gene Expression Omnibus datasets were used to identify differentially expressed genes (DEGs), followed by immune infiltration analysis and machine learning\u2010based gene selection. Key genes were validated using independent datasets and expression quantitative trait loci\u2010MR analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Significant causal links with SLE were observed for 10 immune cell subtypes (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01). A total of 17 DEGs, including FCGR2A, TMEM181, and RASA3, were identified as being associated with immune infiltration. Single\u2010sample gene set enrichment analysis revealed altered immune cell compositions in SLE. Five key genes (FCGR2A, TMEM181, RASA3, BCAR3, and MCTP2) with strong diagnostic potential (area under the curve = 0.948) were identified using a support vector machine model. Their causal relevance was confirmed by MR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This integrative approach revealed 10 immune cell types and five genes with causal roles in SLE, offering novel insights into disease mechanisms and potential targets for precision medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70754","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T05:26:06Z","timestamp":1758086766000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mendelian Randomization and Machine Learning Reveal Immune Cell and Gene Drivers in Systemic Lupus Erythematosus"],"prefix":"10.1002","volume":"15","author":[{"given":"Luofei","family":"Huang","sequence":"first","affiliation":[{"name":"Liuzhou Municipal Liutie Central Hospital  Liuzhou Guangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"shi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine The People's Hospital of Laibin  Laibin Guangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9299-0026","authenticated-orcid":false,"given":"Han","family":"Li","sequence":"additional","affiliation":[{"name":"Liuzhou People's Hospital Affiliated to Guangxi Medical University  Liuzhou Guangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quanzhi","family":"Lin","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi University of Science and Technology  Liuzhou Guangxi 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