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Up to 90% of individuals with tuberous sclerosis complex (TSC) are affected by some type of epilepsy, yet the common variants contributing to epilepsy risk in the general population have not been evaluated in the context of TSC\u2010associated epilepsy. Such knowledge is important to help uncover the underlying pathogenesis of epilepsy in TSC which is not fully understood, and critical as uncontrolled epilepsy is a major problem in this population. To evaluate common genetic modifiers of epilepsy, our study pooled phenotypic and genotypic data from 369 individuals with TSC to evaluate known and novel epilepsy common variants. We did not find evidence of enhanced genetic penetrance for known epilepsy variants identified across the largest genome\u2010wide association studies of epilepsy in the general population, but identified support for novel common epilepsy variants in the context of TSC. Specifically, we have identified a novel signal in <jats:italic>SLC7A1<\/jats:italic> that may be functionally involved in pathways relevant to TSC and epilepsy. Our study highlights the need for further evaluation of genetic modifiers in TSC to aid in further understanding of epilepsy in TSC and improve outcomes.<\/jats:p>","DOI":"10.1002\/ajmg.a.63569","type":"journal-article","created":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T08:34:24Z","timestamp":1708158864000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Common epilepsy variants from the general population are not associated with epilepsy among individuals with tuberous sclerosis complex"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0129-9860","authenticated-orcid":false,"given":"Melissa A.","family":"Richard","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Section of Hematology\u2010Oncology Baylor College of Medicine  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip 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