Underrepresentation in Epilepsy Genome Studies May Increase Health Disparities

Study results presented at the American Epilepsy Society (AES) 2024 Annual Meeting showed a significant lack of diversity in epilepsy genome-wide association studies (GWAS). Most of the participants in these studies were of European ancestry, with an underrepresentation of participants of East Asian and African ancestry, and an absence of participants of South Asian and Native American ancestries. Results also demonstrated that mixed ancestry studies more often identified significant single nucleotide polymorphisms (SNPs) associated with epilepsies.

Researchers analyzed all 68 epilepsy GWAS from the GWAS Catalog (N=3,574,909), including studies on genetic/idiopathic generalized epilepsy and focal epilepsy. Cohorts were screened for sample overlap, and studies were characterized based on ancestry categories included in the 1000 Genomes Project.

• 71.5% of participants were of European ancestry, 14.3% were of East Asian ancestry, 0.5% were of African ancestry, and 0% were of South Asian or Native American ancestry (13.7% of participants had unreported ancestry).
• Among epilepsy cases, only 8% of participants were of non-European ancestry (6.4% East Asian, 1.5% African).
• 98 unique SNPs with genome-wide significance (P<.001) were identified across all studies.
• Studies comprised exclusively of participants of European ancestry made up 66% of all studies but contributed only 21% of significant SNPs that were identified.
• Mixed-ancestry studies comprised 16% of studies and contributed 58% of significant SNPs that were identified.

Researchers noted that the lack of diversity in epilepsy GWAS could exacerbate existing health disparities in epilepsy. The predictive accuracy of polygenic risk scores is poor among underrepresented ancestral groups, and children with epilepsy from historically underrepresented ancestries have higher rates of variants of uncertain significance, both of which impact diagnosis and management of epilepsy.