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

Abstract-Text (inklusive Referenzen und Bildunterschriften)

Introduction

An epilepsy diagnosis has large consequences but is often challenging in clinical practice. Novel biomarkers are thus greatly needed.

Methods

Here, we investigate how common genetic factors (weighted and summed as epilepsy polygenic risk scores, PRS) influence epilepsy risk in detailed longitudinal electronic health records of > 360k Finns spanning up to 50 years of lifetime.

Results

Individuals with a high genetic generalized epilepsy PRS (PRS-GGE) in FinnGen had increased risk for genetic generalized epilepsy (GGE) (hazard ratio [HR] 1.55 per standard deviation [SD] of PRS-GGE) across lifetime and after unspecified seizure events. Within 10 years after an unspecified seizure, the GGE rate was 37% when PRS-GGE > 2 SD compared to 5.6% when PRSGGE < -2 SD. The effect of PRS-GGE was even larger on GGE subtypes of idiopathic generalized epilepsy (IGE) (HR 2.1 per SD PRS-GGE). PRS-GGE had a larger effect on epilepsy when the first seizure event happened at an ealier age. Analogously, we found significant but more modest focal epilepsy PRS burden associated with non-acquired focal epilepsy (NAFE). We found PRS-GGE was specifically associated with GGE in comparison with >2000 other independent diseases of all clinical areas. In contrast, PRS-NAFE was also associated with other diseases than NAFE (i.e. more pleiotropic).

Conclusions

Combined with independent standard clinical risk factors such as an abnormal EEG epilepsy PRSs thus have potential to serve as biomarkers for epilepsy diagnosis.