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

• Published in: Nature communications Vol. 15; no. 1; pp. 6277 - 11
• Main Authors: Heyne, Henrike O., Pajuste, Fanny-Dhelia, Wanner, Julian, Daniel Onwuchekwa, Jennifer I., Mägi, Reedik, Palotie, Aarno, Kälviainen, Reetta, Daly, Mark J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.07.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 45/43; 631/208/721; 692/1807/1693; 692/499; 692/53/2423; 692/617/375/178; Adolescent; Adult; Aged; Biomarkers; Child; Convulsions & seizures; Diagnosis; Electronic Health Records; Electronic medical records; Epilepsies, Partial - genetics; Epilepsy; Epilepsy - epidemiology; Epilepsy - genetics; Epilepsy, Generalized - genetics; Female; Genetic factors; Genetic Predisposition to Disease; Genetic Risk Score; Humanities and Social Sciences; Humans; Longitudinal Studies; Male; Middle Aged; multidisciplinary; Multifactorial Inheritance - genetics; Risk; Risk Factors; Science; Science (multidisciplinary); Seizures; Seizures - genetics; Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-50295-z

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. In this study, the authors showed how common genetic factors in the form of epilepsy polygenic risk scores influence epilepsy risk across lifetime and after unspecified seizure events. This could eventually help epilepsy diagnosis.