Penetrance of pathogenic epilepsy variants is low and shaped by common genetic background
Our results suggest that average variant penetrance is lower than expected and modified by PRS. A high PRS combined with a pathogenic variant may be necessary to develop a severe epilepsy phenotype like DEE. Reconsidering penetrance assumptions could improve variant classification and diagnostic yield. Our findings may enhance genetic counseling by refining risk estimates and could extend to other diseases.
Authors
- Remi Stevelink (ORCID: https://orcid.org/0000-0003-0214-7965)
- Kees P. J. Braun (ORCID: https://orcid.org/0000-0003-3631-0003)
- Bobby P.C. Koeleman (ORCID: https://orcid.org/0000-0001-7749-182X)
- Ruben van ‘t Slot (ORCID: https://orcid.org/0000-0002-0952-0139)
- M. Martijn Piet (ORCID: https://orcid.org/0009-0008-6158-5969)
- Yorgos Bos (ORCID: https://orcid.org/0000-0002-5951-4060)
Institutions
- Utrecht University (NL)
- University Medical Center Utrecht (NL)
Publication Details
- Journal
- Epilepsia
- Published
- 2025-11-14
- DOI
- https://doi.org/10.1111/epi.70018
- Citations
- 1
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.82