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.

癫痫的诊断对个人有重大影响，但在临床实践中往往具有挑战性。因此非常需要新的生物标志物。在这里，我们研究了超过 70 万芬兰人和爱沙尼亚人的详细纵向电子健康记录 (EHR) 中常见的遗传因素（癫痫多基因风险评分，[PRS]）如何影响癫痫风险。我们发现，高遗传性全身性癫痫 PRS (PRS _GGE ) 会增加一生中以及未明确的癫痫发作事件后 10 年内患遗传性全身性癫痫 (GGE) 的风险（每个 PRS _GGE标准差 [SD] 的风险比 [HR] 1.73）。 PRS _GGE对女性特发性全身性癫痫和早期癫痫发作的影响显着更大。类似地，我们发现局灶性癫痫 PRS 负担与非获得性局灶性癫痫 (NAFE) 相关，但显着但较为温和。在这里，我们概述了癫痫特异性 PRS 作为首次癫痫发作事件后生物标志物的潜力。