Faculty, Staff and Student Publications
Publication Date
6-1-2024
Journal
American Journal of Medical Genetics Part A
Abstract
Common genetic variants identified in the general population have been found to increase phenotypic risks among individuals with certain genetic conditions. 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-associated 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-wide 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 SLC7A1 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.
Keywords
Humans, Tuberous Sclerosis, Epilepsy, Female, Genome-Wide Association Study, Male, Genetic Predisposition to Disease, Adult, Genetic Variation, Genotype, Adolescent, Phenotype, Child, Polymorphism, Single Nucleotide, Child, Preschool, tuberous sclerosis complex, epilepsy, genetic modifiers, common variants
DOI
10.1002/ajmg.a.63569
PMID
38366765
PMCID
PMC11060940
PubMedCentral® Posted Date
6-1-2025
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes