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Polygenic risk scores as a marker for epilepsy risk across lifetime and after unspecified seizure events

Author

Listed:
  • Henrike O. Heyne

    (University of Potsdam
    Mount Sinai School of Medicine
    University of Helsinki
    Broad Institute of MIT and Harvard)

  • Fanny-Dhelia Pajuste

    (University of Tartu
    University of Tartu)

  • Julian Wanner

    (University of Potsdam
    University of Helsinki)

  • Jennifer I. Daniel Onwuchekwa

    (University of Potsdam
    University of Siegen)

  • Reedik Mägi

    (University of Tartu
    University of Tartu)

  • Aarno Palotie

    (University of Helsinki
    Broad Institute of MIT and Harvard
    Broad Institute of MIT and Harvard)

  • Reetta Kälviainen

    (Member of ERN EpiCARE
    University of Eastern Finland)

  • Mark J. Daly

    (University of Helsinki
    Broad Institute of MIT and Harvard
    Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

Abstract

A diagnosis of epilepsy has significant consequences for an individual but is often challenging in clinical practice. Novel biomarkers are thus greatly needed. Here, we investigated how common genetic factors (epilepsy polygenic risk scores, [PRSs]) influence epilepsy risk in detailed longitudinal electronic health records (EHRs) of > 700k Finns and Estonians. We found that a high genetic generalized epilepsy PRS (PRSGGE) increased risk for genetic generalized epilepsy (GGE) (hazard ratio [HR] 1.73 per PRSGGE standard deviation [SD]) across lifetime and within 10 years after an unspecified seizure event. The effect of PRSGGE was significantly larger on idiopathic generalized epilepsies, in females and for earlier epilepsy onset. Analogously, we found significant but more modest focal epilepsy PRS burden associated with non-acquired focal epilepsy (NAFE). Here, we outline the potential of epilepsy specific PRSs to serve as biomarkers after a first seizure event.

Suggested Citation

  • Henrike O. Heyne & Fanny-Dhelia Pajuste & Julian Wanner & Jennifer I. Daniel Onwuchekwa & Reedik Mägi & Aarno Palotie & Reetta Kälviainen & Mark J. Daly, 2024. "Polygenic risk scores as a marker for epilepsy risk across lifetime and after unspecified seizure events," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50295-z
    DOI: 10.1038/s41467-024-50295-z
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    References listed on IDEAS

    as
    1. Tian Ge & Chia-Yen Chen & Yang Ni & Yen-Chen Anne Feng & Jordan W. Smoller, 2019. "Polygenic prediction via Bayesian regression and continuous shrinkage priors," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    2. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "Author Correction: FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 615(7952), pages 19-19, March.
    3. Nina Mars & Elisabeth Widén & Sini Kerminen & Tuomo Meretoja & Matti Pirinen & Pietro della Briotta Parolo & Priit Palta & Aarno Palotie & Jaakko Kaprio & Heikki Joensuu & Mark Daly & Samuli Ripatti, 2020. "The role of polygenic risk and susceptibility genes in breast cancer over the course of life," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    4. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 613(7944), pages 508-518, January.
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