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. 2022 Sep 22;34(3):225-230.
doi: 10.1515/medgen-2022-2146. eCollection 2022 Oct.

Polygenic risk scores in epilepsy

Henrike O Heyne  1   2   3   4   5
Affiliations

Polygenic risk scores in epilepsy

Henrike O Heyne. Med Genet. .

Abstract

An epilepsy diagnosis has large consequences for an individual but is often difficult to make in clinical practice. Novel biomarkers are thus greatly needed. Here, we give an overview of how thousands of common genetic factors that increase the risk for epilepsy can be summarized as epilepsy polygenic risk scores (PRS). We discuss the current state of research on how epilepsy PRS can serve as a biomarker for the risk for epilepsy. The high heritability of common forms of epilepsy, particularly genetic generalized epilepsy, indicates a promising potential for epilepsy PRS in diagnosis and risk prediction. Small sample sizes and low ancestral diversity of current epilepsy genome-wide association studies show, however, a need for larger and more diverse studies before epilepsy PRS could be properly implemented in the clinic.

Keywords: complex disease; epilepsy; genome-wide association study; polygenic score; risk prediction.

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Conflict of interest statement

Competing interests: Authors state no conflict of interest.

Figures

Figure 1
Figure 1
Adapted from [12]. Heritability estimates for different brain disorders. Red bars denote psychiatric disorders, while blue bars denote neurological disorders. ADHD – attention deficit hyperactivity disorder; ASD – autism spectrum disorder; ICH – intracerebral hemorrhage; OCD – obsessive-compulsive disorder; MDD – major depressive disorder; PTSD – post-traumatic stress disorder. Error bars show one standard error.
Figure 2
Figure 2
The number of cases in recent GWAS across different disease areas. Many common diseases have GWAS sample sizes of >100,000, while the largest GWAS in focal epilepsy (n=9,671) and generalized epilepsy (n=3,769) are substantially smaller at the time of writing.
Figure 3
Figure 3
Calculation of epilepsy PRS. (A) First, genetic differences between the groups of individuals with and without epilepsy are identified in a genome-wide association study (GWAS). A GWAS finds genetic markers that decrease or increase the risk for epilepsy. (B) In a second independent target cohort, thousands of epilepsy risk or protective markers are then weighted and counted in each individual to obtain a single number representing the overall genetic liability for epilepsy: the epilepsy PRS. (C) On a group level, the epilepsy PRS (or genetic burden for epilepsy) can then be compared between epilepsy cases and controls in the target cohort.
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