{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T10:11:50Z","timestamp":1773915110914,"version":"3.50.1"},"reference-count":82,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T00:00:00Z","timestamp":1755388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260865"],"award-info":[{"award-number":["82260865"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Epidemiological data indicates that individuals with epilepsy exhibit an elevated susceptibility to autoimmune disorders, and conversely, those with systemic autoimmune diseases (SAD) demonstrate a heightened predisposition to epilepsy. Although an increasing number of publications support this association, the causal direction remains undetermined. This investigation offers evidence supporting a causal relationship between these conditions through a bidirectional two\u2010sample Mendelian randomization (MR) analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bidirectional two\u2010sample MR analyses were performed to investigate the causal relationships and directionality between various epilepsy subtypes and eight SAD. The analysis utilized genome\u2010wide association study (GWAS) summary data for the following conditions: type 1 diabetes, systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), rheumatoid arthritis, coeliac disease, multiple sclerosis (MS), ulcerative colitis, and Crohn's disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In this study, causal analyses were performed for different epilepsy subtypes and SAD disorders. In the Inverse\u2010Variance Weighted (IVW) model, the MR study indicated that focal epilepsy increased the risk of IBD [odds ratio (OR): 1.15, confidence interval (CI): 1.02\u20131.30,\n                      <jats:italic>p<\/jats:italic>\n                      : 0.027] and MS [OR: 1.25, CI: 1.07\u20131.47,\n                      <jats:italic>p<\/jats:italic>\n                      : 0.004]. Childhood absence epilepsy increased the risk of MS [OR: 0.25, CI: 0.07\u20130.90,\n                      <jats:italic>p<\/jats:italic>\n                      : 0.034]. Reverse analyses showed that SLE increased the risk of myoclonic epilepsy in adolescents [OR: 1.01, CI: 1.00\u20131.01,\n                      <jats:italic>p<\/jats:italic>\n                      : 0.042], and IBD [OR: 0.99, CI: 0.99\u20131.00,\n                      <jats:italic>p<\/jats:italic>\n                      : 0.013], and celiac disease [OR: 0.99, CI: 0.99\u20131.00,\n                      <jats:italic>p<\/jats:italic>\n                      : 0.021] reduced the risk of generalized epilepsy. The results demonstrated homogeneity, and the MR\u2010Egger directions were concordant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>This study shows that epilepsy is a causal risk factor for both IBD and MS, providing new insights into the prevention of SAD in people with epilepsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>This paper employs a bidirectional two\u2010sample MR analysis to investigate the genetic correlation between epilepsy and autoimmune diseases, revealing potential associations between the onset of epilepsy and MS as well as IBD. Further exploration in this area requires support from clinical data.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70102","type":"journal-article","created":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T16:40:08Z","timestamp":1755448808000},"page":"1415-1425","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Epilepsy and systemic autoimmune diseases: A\u00a0bidirectional two\u2010sample Mendelian randomization study"],"prefix":"10.1002","volume":"10","author":[{"given":"Ruoshi","family":"Tian","sequence":"first","affiliation":[{"name":"School of Bioengineering Zunyi Medical University  Zhuhai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenlong","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Zunyi Medical University  Zunyi Guizhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqing","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Bioengineering Zunyi Medical University  Zhuhai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Bioengineering Zunyi Medical University  Zhuhai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0287-3828","authenticated-orcid":false,"given":"Xirui","family":"He","sequence":"additional","affiliation":[{"name":"School of Bioengineering Zunyi Medical University  Zhuhai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,17]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32596-0"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30360-5"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-52898-8.00006-9"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13653"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2014.09.003"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.081420.x"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60899-5"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000013068"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.107429"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12014"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02106.x"},{"issue":"43","key":"e_1_2_13_13_1","first-page":"849","article-title":"Comorbidity in adults with epilepsy\u2013United States, 2010","volume":"62","author":"Centers for Disease Control and Prevention (CDC)","year":"2013","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201542"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.14126"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00225-2"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002390"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003424"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2020.111393"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.5698\/1535-7511.17.3.134"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12444"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0217-x"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa362"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.11.012"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-022-01826-9"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.188"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2018.12.006"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2016.08.003"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03030.x"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/155005949502600211"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09332-x"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1389549"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2004.17504.x"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(19)30055-0"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000517352"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2009.02.009"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016010098"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07524-z"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13709"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06250-x"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03552-w"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3434"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3760"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00931-x"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.543"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav7188"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1346"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.105148"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004740"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1986.tb03602.x"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2011-300414"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2021.113946"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2008.00177.x"},{"issue":"4","key":"e_1_2_13_56_1","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1093\/brain\/awm038","article-title":"Meningeal B\u2010cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology","volume":"130","author":"Magliozzi R","year":"2007","journal-title":"Brain"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.2015.1079130"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.04.020"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13232014"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.362"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izae012"},{"issue":"4","key":"e_1_2_13_62_1","first-page":"105","article-title":"Causal relationship between inflammatory bowel disease and epilepsy: evidence from genetic correlation and Mendelian randomization study","volume":"19","author":"Min H","year":"2023","journal-title":"J Neurol Neurorehabil"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i1.91"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10209"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.742449"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2017.1290757"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.994270"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1128\/Spectrum.00483-21"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16091289"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14077"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01453.x"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203318763533"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-018-0156-8"},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000165959.98370.D5"},{"key":"e_1_2_13_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08099-3"},{"key":"e_1_2_13_76_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/745647"},{"key":"e_1_2_13_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12664-021-01215-2"},{"key":"e_1_2_13_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14160"},{"key":"e_1_2_13_79_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182544728"},{"key":"e_1_2_13_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2018.09.004"},{"key":"e_1_2_13_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2017.05.027"},{"key":"e_1_2_13_82_1","doi-asserted-by":"publisher","DOI":"10.1111\/acps.13554"},{"key":"e_1_2_13_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14470"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.70102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T10:32:26Z","timestamp":1764671546000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.70102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,17]]},"references-count":82,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/epi4.70102"],"URL":"https:\/\/doi.org\/10.1002\/epi4.70102","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,17]]},"assertion":[{"value":"2025-01-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}