Genetic dissection of the common epilepsies
- 1 April 2006
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Neurology
- Vol. 19 (2), 157-163
- https://doi.org/10.1097/01.wco.0000218232.66054.46
Abstract
Only two functionally validated susceptibility genes, CACNA1H and GABRD, have so far been identified in the common epilepsies using a candidate gene approach. The difficulty with the alternative statistical approach, where none of the suggested candidates has been functionally validated, may partly be due to the posited genetic architecture of the common epilepsies, such as the idiopathic generalized epilepsies. A subset of both rare and common variants from a much larger pool of susceptibility genes may contribute to disease risk. We review methods and designs for the genetic dissection of common epilepsies. Genetic association studies, though theoretically more powerful than linkage analysis, have not yet delivered validated susceptibility genes. Methodological flaws can undermine such studies but are correctable. Concerns remain, however, about the extent of underlying genetic heterogeneity in common epilepsies. Genome-wide association studies are increasingly feasible, but issues remain about their conduct and analysis. Meta-analysis may resolve conflicting association studies, facilitated by the establishment of databases of genetic association studies. Newer multi-locus and admixture mapping approaches are attractive alternatives to traditional association studies and may offer new insights into identifying epilepsy genes. We conclude by emphasizing the importance of deeper endophenotyping using electroclinical, imaging, and molecular approaches to dissect the common epilepsies.Keywords
This publication has 70 references indexed in Scilit:
- Susceptibility genes for complex epilepsyHuman Molecular Genetics, 2005
- Gene–environment interactions in human diseasesNature Reviews Genetics, 2005
- Partners in crimeNature Genetics, 2005
- Genetic Association Studies in Epilepsy: “The Truth Is Out There”Epilepsia, 2004
- Fever, genes, and epilepsyThe Lancet Neurology, 2004
- Monogenic idiopathic epilepsiesThe Lancet Neurology, 2004
- Channelopathies as a genetic cause of epilepsyCurrent Opinion in Neurology, 2003
- The allelic architecture of human disease genes: common disease-common variant... or not?Human Molecular Genetics, 2002
- The allelic structure of common diseaseHuman Molecular Genetics, 2002
- On the allelic spectrum of human diseaseTrends in Genetics, 2001