Flickering lights, endophenotypes, and EEG genetics – CHD2 in photosensitivity

Heritable. Many epilepsy syndromes have signature EEG traits, and these traits are thought to have a strong genetic component. The endophenotype concept suggests that using these epilepsy-related traits in genetic studies will facilitate gene discovery, a concept that has failed us so far in epilepsy research, unfortunately. Now, in a recent publication in Brain, we were able to demonstrate that variants in CHD2 predispose to photosensitivity, an abnormal cortical response to flickering light. Finally, after several decades of persisting difficulties, there is some progress in the field of EEG genetics. Continue reading

A polygenic trickle of rare disruptive variants in schizophrenia

Polygenic. Schizophrenia is a complex neurodevelopmental disorder that is assumed to be caused by a mixture of genetic and non-genetic factors. The genetic component in schizophrenia is thought to be polygenic, i.e. due to the interaction of multiple genetic factors. Rare variants may play a particular role in this presumable polygenic genetic architecture, but so far this component of the genetic morbidity has been hard to pin down. Now, a recent study in Nature explores the role of rare, disruptive mutations in schizophrenia using large-scale population-based exome sequencing. Let’s find out about a new level of exome-wide honesty and why even a gene with 10 disruptive mutations in cases and none in controls is only mentioned in passing. Continue reading

Malaria, seizures and genes

Our old genome. When talking about seizures and genes, “malaria” is usually not the first thing that comes to mind. However, malaria-associated seizures are a major cause of neurological disability in Sub-Saharan Africa. Given the frequency of malaria infections on a worldwide scale, Plasmodium falciparum, the parasite causing malaria, is probably one of the most frequent causes of acute seizures. Our genome has adapted to dealing with parasites over evolutionary time and several disease-causing mutations are thought to be relatively frequent, as they also confer resistance to malaria. For malaria-associated seizures, family studies show an increase in epilepsy in relatives, suggesting that these parasite-induced epileptic seizures may also have a genetic predisposition. A recent study in Epilepsia now investigates malaria candidate polymorphisms as genetic risk factors for malaria-associated seizures. Continue reading

Cold fusion – joining exome datasets to identify autism genes

Mergers and acquisitions. Invariably, genetic research in neurodevelopmental disorders is moving towards joint analyses of large datasets. While the methodology of meta-analysis is well established for genome-wide association studies, the joint analysis of exome datasets comes with many question marks. Now, a recent paper in PLOS Genetics pioneers the field of joint exome data analysis for association studies in autism. This paper highlights some unexpected facets of rare variant analysis. Continue reading