Journal Article

Failure to replicate previously reported genetic associations with sporadic temporal lobe epilepsy: where to from here?

Gianpiero L. Cavalleri, John M. Lynch, Chantal Depondt, Mari-Wyn Burley, Nicholas W. Wood, Sanjay M. Sisodiya and David B. Goldstein

in Brain

Published on behalf of The Guarantors of Brain

Volume 128, issue 8, pages 1832-1840
Published in print August 2005 | ISSN: 0006-8950
Published online May 2005 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awh524
Failure to replicate previously reported genetic associations with sporadic temporal lobe epilepsy: where to from here?

Show Summary Details

Preview

Temporal lobe epilepsy (TLE), traditionally thought to develop largely due to environmental factors, has recently become the focus of association studies in an effort to determine genetic risk factors. Here we examine all previous claims of association of genetic polymorphisms with TLE by attempting replication in a cohort of 339 TLE patients of European origin. We also examine if these variants contribute to other types of epilepsy by examination in a larger cohort of 752 patients representing a range of different epilepsies. We fail to clearly replicate any of the previously reported associations and also fail to show a role for these variants in the development of other forms of epilepsy. Although our results cannot definitively rule out a role for these genes, they do suggest that most and perhaps all of the previous associations are false positives. As has been the experience with other diseases, these results highlight the importance of larger sample sizes and replication. In TLE, it appears that collaboration before publication is the best option to increase sample size sufficiently in the short term. These general principles are applicable to other studies undertaken for common complex diseases.

Keywords: epilepsy; TLE; epilepsy genetics; association; replication; FS = febrile seizures; HS = hippocampal sclerosis; IGE = idiopathic generalized epilepsy; TLE = temporal lobe epilepsy

Journal Article.  6555 words. 

Subjects: Neurology ; Neuroscience

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.