Polygenic Risk Scores As a Marker for Epilepsy Risk Across Lifetime and After Unspecified Seizure Events

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jul 25

PMID 39054313

Authors

Henrike O Heyne

Fanny-Dhelia Pajuste

Julian Wanner

Jennifer I Daniel Onwuchekwa

Reedik Magi

Aarno Palotie

Reetta Kalviainen

Mark J Daly

Affiliations

Soon will be listed here.

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 (PRS) increased risk for genetic generalized epilepsy (GGE) (hazard ratio [HR] 1.73 per PRS standard deviation [SD]) across lifetime and within 10 years after an unspecified seizure event. The effect of PRS 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.

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

Heyne H, Pajuste F, Wanner J, Daniel Onwuchekwa J, Magi R, Palotie A Nat Commun. 2024; 15(1):6277.

PMID: 39054313 PMC: 11272783. DOI: 10.1038/s41467-024-50295-z.

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