Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov;61(11):e179-e185.
doi: 10.1111/epi.16717. Epub 2020 Oct 14.

Polygenic risk heterogeneity among focal epilepsies

Affiliations

Polygenic risk heterogeneity among focal epilepsies

Marie Gramm et al. Epilepsia. 2020 Nov.

Abstract

Focal epilepsy (FE) is clinically highly heterogeneous. It has been shown recently that not only rare but also a subset of common genetic variants confer risk for FE. The relatively modest power of genetic studies in FE suggests a high genetic heterogeneity of FE when grouped as one disorder. We hypothesize that the clinical heterogeneity of FE is correlated with genetic heterogeneity on a common risk variant level. To test the hypothesis, we used an FE polygenic risk score "FE-PRS" that combines small effect sizes of thousands of common variants from the largest FE-GWAS (genome-wide association study) into a single measure. We grouped 414 individuals with FE according to common clinical features into subgroups, either by one feature at a time or by all features combined in a cluster analysis. We examined their association with FE-PRS compared to 20 435 matched population controls and observed heterogeneous FE-PRS burden among the subgroups. The highest phenotypic variance explained by FE-PRS was identified in a cluster analysis-defined FE subgroup where all individuals had unknown etiologies and psychiatric comorbidities, and the majority had early onset seizures. Our results indicate that genetic factors associated with FE have differential burden among FE subtypes. Future studies using better-powered FE-PRS might have clinical utility.

Keywords: clustering; focal epilepsy; genetics; polygenic risk.

PubMed Disclaimer

Similar articles

Cited by

  • ASSOCIATIONS BETWEEN EPILEPSY-RELATED POLYGENIC RISK AND BRAIN MORPHOLOGY IN CHILDHOOD.
    Ngo A, Liu L, Larivière S, Kebets V, Fett S, Weber CF, Royer J, Yu E, Rodríguez-Cruces R, Zhang Z, Ooi LQR, Thomas Yeo BT, Frauscher B, Paquola C, Caligiuri ME, Gambardella A, Concha L, Keller SS, Cendes F, Yasuda CL, Bonilha L, Gleichgerrcht E, Focke NK, Kotikalapudi R, O'Brien TJ, Sinclair B, Vivash L, Desmond PM, Lui E, Vaudano AE, Meletti S, Kälviäinen R, Soltanian-Zadeh H, Winston GP, Tiwari VK, Kreilkamp BAK, Lenge M, Guerrini R, Hamandi K, Rüber T, Bauer T, Devinsky O, Striano P, Kaestner E, Hatton SN, Caciagli L, Kirschner M, Duncan JS, Thompson PM; ENIGMA Consortium Epilepsy Working Group; McDonald CR, Sisodiya SM, Bernasconi N, Bernasconi A, Gan-Or Z, Bernhardt BC. Ngo A, et al. bioRxiv [Preprint]. 2025 Jan 17:2025.01.17.633277. doi: 10.1101/2025.01.17.633277. bioRxiv. 2025. PMID: 39868179 Free PMC article. Preprint.
  • Defective lipid signalling caused by mutations in PIK3C2B underlies focal epilepsy.
    Gozzelino L, Kochlamazashvili G, Baldassari S, Mackintosh AI, Licchetta L, Iovino E, Liu YC, Bennett CA, Bennett MF, Damiano JA, Zsurka G, Marconi C, Giangregorio T, Magini P, Kuijpers M, Maritzen T, Norata GD, Baulac S, Canafoglia L, Seri M, Tinuper P, Scheffer IE, Bahlo M, Berkovic SF, Hildebrand MS, Kunz WS, Giordano L, Bisulli F, Martini M, Haucke V, Hirsch E, Pippucci T. Gozzelino L, et al. Brain. 2022 Jul 29;145(7):2313-2331. doi: 10.1093/brain/awac082. Brain. 2022. PMID: 35786744 Free PMC article.
  • Investigation of epilepsy-related genes in a Drosophila model.
    Qu X, Lai X, He M, Zhang J, Xiang B, Liu C, Huang R, Shi Y, Qiao J. Qu X, et al. Neural Regen Res. 2026 Jan 1;21(1):195-211. doi: 10.4103/NRR.NRR-D-24-00877. Epub 2024 Dec 16. Neural Regen Res. 2026. PMID: 39688550 Free PMC article.
  • Epilepsy Genetics and Precision Medicine in Adults: A New Landscape for Developmental and Epileptic Encephalopathies.
    Beltrán-Corbellini Á, Aledo-Serrano Á, Møller RS, Pérez-Palma E, García-Morales I, Toledano R, Gil-Nagel A. Beltrán-Corbellini Á, et al. Front Neurol. 2022 Feb 17;13:777115. doi: 10.3389/fneur.2022.777115. eCollection 2022. Front Neurol. 2022. PMID: 35250806 Free PMC article. Review.

References

REFERENCES

    1. Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon C-S, Dykeman J, et al. Prevalence and incidence of epilepsy. Neurology. 2017;88:296-303.
    1. Skidmore C. Adult focal epilepsies. Continuum: lifelong learning. Neurology. 2016;22:94-115.
    1. Perucca P. Genetics of focal epilepsies: what do we know and where are we heading? Epilepsy Curr. 2018;18:356-62.
    1. Kasperavičiūtė D, Catarino CB, Matarin M, Leu C, Novy J, Tostevin A, et al. Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A. Brain. 2013;136:3140-50.
    1. Guo Y, Baum LW, Sham PC, Wong V, Ng PW, Lui CHT, et al. Two-stage genome-wide association study identifies variants in CAMSAP1L1 as susceptibility loci for epilepsy in Chinese. Hum Mol Genet. 2012;21:1184-9.

Publication types

LinkOut - more resources