Progress from genome-wide association studies and copy number variant studies in epilepsy

The pace of gene discovery in epilepsy remains frenetic. Although most recent discoveries have come from next-generation sequencing studies, there has also been important progress using more established methodologies, such as genome-wide association studies (GWASs) and copy number variants (CNVs) identified through array-based techniques. Progress in these areas over the last year is reviewed.

The first meta-analysis of GWASs was a landmark development for the epilepsy community, though more sizeable studies are sorely needed. Other GWASs point to potentially interesting discoveries, and are in need of replication and follow-up. Copy number variation is emerging as an important genetic contribution to causation across a wide range of epilepsies, with a number of discoveries in epilepsies from the common, such as genetic generalized epilepsies, to the individually comparatively rare, such as particular epileptic encephalopathies. The first studies of CNV analysis from next-generation sequencing data, and of the combination of sequencing and array-based data, have also emerged, allowing more comprehensive genetic evaluation of specific phenotypes.

GWASs based on single nucleotide polymorphisms, and CNV analyses based on a variety of data sources, retain a place in the discovery of causation and susceptibility in the epilepsies, and will probably become more powerful in the near future through the use of large-scale next-generation sequencing studies. There are still discoveries to come through these routes.