PRS. While monogenic epilepsies are the main genetic etiologies diagnosed in clinical practice, the majority of the genetic epilepsies is not explained by single, strong genes. In contrast, on a population level, the main genetic risk for epilepsy is explained by common genetic variants. While these variants had been largely inaccessible in the past, recent studies have been successful in identifying these variants and understanding the joint risk for epilepsy that are conferred by multiple genetic factors. When assigned to individuals, this joint risk is typically measured as polygenic risk scores. In a recent study, we demonstrate that this finding extends to familial epilepsies, which are highly enriched for extreme polygenic scores. However, in the very moment that I was trying to type the first lines of this blog post, a similar study in schizophrenia appeared online, showing exactly the opposite. Here are some thoughts on why polygenic risk is not as straightforward as you would expect. Continue reading →