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

Autor: Heyne HO; Hasso Plattner Institute for Digital Engineering, University of Potsdam, Potsdam, Germany. henrike.heyne@hpi.de.; Hasso Plattner Institute, Mount Sinai School of Medicine, New York, NY, US. henrike.heyne@hpi.de.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. henrike.heyne@hpi.de.; Program for Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. henrike.heyne@hpi.de., Pajuste FD; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia., Wanner J; Hasso Plattner Institute for Digital Engineering, University of Potsdam, Potsdam, Germany.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland., Daniel Onwuchekwa JI; Hasso Plattner Institute for Digital Engineering, University of Potsdam, Potsdam, Germany.; Faculty of Life Sciences, University of Siegen, Siegen, Germany., Mägi R; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia., Palotie A; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.; Program for Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Kälviainen R; Kuopio Epilepsy Center, Neurocenter, Kuopio University Hospital, Member of ERN EpiCARE, Kuopio, Finland.; Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland., Daly MJ; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.; Program for Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 25; Vol. 15 (1), pp. 6277. Date of Electronic Publication: 2024 Jul 25.
DOI: 10.1038/s41467-024-50295-z
Abstrakt: 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 (PRS GGE ) increased risk for genetic generalized epilepsy (GGE) (hazard ratio [HR] 1.73 per PRS GGE standard deviation [SD]) across lifetime and within 10 years after an unspecified seizure event. The effect of PRS GGE 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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