Predictive value of the polygenic risk score for developing epilepsy: a systematic review and meta-analysis

Purpose: This study aimed to integrate the findings of previous studies to clarify the predictive value of the polygenic risk score (PRS) for epilepsy. Methods: The MEDLINE, EMBASE, and CENTRAL databases were systematically searched for studies investigating PRS in epilepsy. Additionally, a meta-analysis was performed using random-effects models of studies that included PRS calculations using similar methodologies. The main outcome was the odds ratio (OR) for developing epilepsy based on the generalized or focal epilepsy PRS. The risk of bias (Q-Genie tool) and heterogeneity between the studies were also assessed. Results: Overall, 585 records were retrieved on April 27, 2024. Eleven studies were included in this systematic review. Most studies were conducted on cohorts with European ancestry. The risk of developing epilepsy increased with a higher PRS, which was more pronounced in patients with generalized epilepsy. The total Q-Genie tool score of the included studies was 50.9 (good quality: >45). The meta-analysis included two studies and found that the ORs for generalized epilepsy were 2.18 (95 % confidence interval [CI] 1.91–2.48), 2.65 (95 % CI 2.07–3.39), and 4.62 (95 % CI 3.45–6.20) for the top 20 %, 5 %, and 0.5 % of the PRS distribution, respectively; the respective ORs for focal epilepsy were 1.19 (95 % CI 0.84–1.67), 1.40 (95 % CI 1.28–1.52), and 1.69 (95 % CI 1.27–2.24). Significant heterogeneity was found only in the top 20 % of PRS cases for focal epilepsy (I² = 97.0 %; Q test p < 0.0001). Conclusion: The PRS could be an effective tool for predicting development of epilepsy.