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Seizure remission was defined as being 5 and 10\u2009years seizure\u2010free at last observation. Total number of tonic\u2013clonic seizures was dichotomized at &lt;4 and \u22654 seizures. Seizure control in patients taking antiseizure medication was defined as no seizures for 1, 2, and 3\u2009years. We used Bayesian generalized linear mixed\u2010effects model (GLMM) to estimate the intraclass correlation coefficient (ICC) of the family\u2010specific random effect, controlling for epilepsy type, age at epilepsy onset, and age at last data collection as fixed effects. We analyzed each cohort separately and performed meta\u2010analysis using GLMMs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The combined cohorts included 3644 individuals with epilepsy from 1463 families. A history of \u22654 tonic\u2013clonic seizures showed strong familial aggregation in three separate cohorts and meta\u2010analysis (ICC .28, 95% confidence interval [CI] .21\u2013.35, Bayes factor 8\u2009\u00d7\u200910<jats:sup>16<\/jats:sup>). Meta\u2010analyses did not reveal significant familial aggregation of seizure remission (ICC .08, 95% CI .01\u2013.17, Bayes factor 1.46) or seizure control for individuals taking antiseizure medication (ICC .13, 95% CI 0\u2013.35, Bayes factor 0.94), with heterogeneity among cohorts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>A history of \u22654 tonic\u2013clonic seizures aggregated strongly in families, suggesting a genetic influence, whereas seizure remission and seizure control for individuals taking antiseizure medications did not aggregate consistently in families. Different seizure outcomes may have different underlying biology and risk factors. These findings should inform the future molecular genetic studies of seizure outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.18004","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T10:55:20Z","timestamp":1715597720000},"page":"2030-2040","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Familial aggregation of seizure outcomes in four familial epilepsy cohorts"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2152-8106","authenticated-orcid":false,"given":"Colin A.","family":"Ellis","sequence":"first","affiliation":[{"name":"Department of Neurology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, &amp; Informatics University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-6153","authenticated-orcid":false,"given":"Karen L.","family":"Oliver","sequence":"additional","affiliation":[{"name":"Department of Medicine, Epilepsy Research Centre University of Melbourne, Austin Health  Melbourne Victoria Australia"},{"name":"Population Health and Immunity Division The Walter and Eliza Hall Institute of Medical Research  Melbourne Victoria Australia"},{"name":"Department of Medical Biology The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7188-522X","authenticated-orcid":false,"given":"Heather C.","family":"Mefford","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology St Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Allen","family":"Hauser","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epidemiology, and the Gertrude H. 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