Epileptic seizures are episodes that can vary from brief, nearly undetectable, periods to long periods of vigorous shaking, which can result in injury in addition to the effect of the seizure on the brain. According to the World Health Organization (WHO), epilepsy affects people of all ages and is the most common chronic brain disease globally. More than 50 million people have epilepsy; nearly 80% of them live in low- and middle-income countries. Comorbidities can include neurological and psychiatric conditions including major depression and anxiety.
Polygenic risk scores (PRS) are a quantitative measure of an individual’s genetic risk of disease. A new study led by Dennis Lal of the Broad Institute of Harvard and M.I.T, USA, used polygenic risk scores (PRS) to examine the pleiotropic effects, when changes in one gene affect multiple phenotypic characteristics, that are associated with epilepsy. They examined associations with both brain function and morphology using the UK biobank dataset. The results were published in the journal PLoS One.
The two main epilepsy syndromes are called generalized epilepsy (GE) and focal epilepsy (FE). GE seizures involve both hemispheres of the brain, whereas FE seizures occur from only one. Seven traits were associated with GE; five personality traits of neuroticism, having smoked at some point, and not having a college or university degree, which had the smallest effect size.
FE risk was strongly associated with low educational attainment, mood swings, having smoked at some point, and episodes of anxiety & depression.
Brain morphology data was obtained from 16,612 UK Biobank participants who underwent magnetic resonance imaging (MRI). GE and FE morphological patterns of cortical thickness and surface area correlated weakly.
The finding of an association between epilepsy and neuroticism was unique to this study. It may reflect novel insights from the methodology and also the fact that neuroticism is also linked with educational attainment and depression, already known correlates of epilepsy.
Generalizability of the results to individuals of non-European ancestry remains to be determined. The UK Biobank is made up of individuals with overall “healthy traits” above the UK average as a whole. Those with epilepsy are likely to be less inclined to participate, so the epilepsy dataset is of limited size and not enriched. Studies specifically designed for those with epilepsy could yield a greater depth of insight. The side effects of epilepsy medications can confound statistical associations, which should be considered.
“Using genetics to dissect the heterogeneous clinical representation of individuals with epilepsy represents a new research area. Potentially, polygenic risk for epilepsy includes genetic factors that predispose to a general vulnerability for altered brain function, which is shared with epilepsy comorbid disorders. Our results provide an initial indication of the opportunities and limitations using PRS research in epilepsy,” concluded the authors.