Blinders, phenotype, and fashionable genetic analysis: A critical examination of the current state of epilepsy genetic studies
Article first published online: 10 JAN 2011
Wiley Periodicals, Inc. © 2010 International League Against Epilepsy
Volume 52, Issue 1, pages 1–9, January 2011
How to Cite
Greenberg, D. A. and Subaran, R. (2011), Blinders, phenotype, and fashionable genetic analysis: A critical examination of the current state of epilepsy genetic studies. Epilepsia, 52: 1–9. doi: 10.1111/j.1528-1167.2010.02734.x
- Issue published online: 10 JAN 2011
- Article first published online: 10 JAN 2011
- Accepted July 29, 2010.
- Genetic analysis;
- Genetic heterogeneity;
- Psychiatric genetics
Although it is accepted that idiopathic generalized epilepsy (IGE) is strongly, if not exclusively, influenced by genetic factors, there is little consensus on what those genetic influences may be, except for one point of agreement: epilepsy is a “channelopathy.” This point of agreement has continued despite the failure of studies investigating channel genes to demonstrate the primacy of their influence on IGE expression. The belief is sufficiently entrenched that the more important issues involving phenotype definition, data collection, methods of analysis, and the interpretation of results have become subordinate to it. The goal of this article is to spark discussion of where the study of epilepsy genetics has been and where it is going, suggesting we may never get there if we continue on the current road. We use the long history of psychiatric genetic studies as a mirror and starting point to illustrate that only when we expand our outlook on how to study the genetics of the epilepsies, consider other mechanisms that could lead to epilepsy susceptibility, and, especially, focus on the critical problem of phenotype definition, will the major influences on common epilepsy begin to be understood.