Evaluating candidate genes in common epilepsies and the nature of evidence

  • Pal D
  • Strug L
  • Greenberg D
  • 22


    Mendeley users who have this article in their library.
  • 11


    Citations of this article.


Very few genetic associations for idiopathic epilepsy have been replicated and this has tempered enthusiasm for the results of genetic studies in epilepsy. What are the reasons for lack of replication? While type 1 error, population stratification, and multiple testing have been discussed extensively, the importance of genetic heterogeneity has been relatively neglected. In the first part of this review, we explore the sources of genetic heterogeneity and their importance for epilepsy genetic studies. In the second part, we review alternatives to the simple law of replication, revisiting Bradford Hill's guidelines for evidence of causality. A coherence perspective is applied to three examples. We conclude that adopting the perspective of integrating coherent and consistent evidence from different experimental approaches is a more appropriate requirement for proceeding to functional studies.

Author-supplied keywords

  • Association studies
  • Causality
  • Epidemiology
  • Evidence
  • Genetic heterogeneity
  • Genetics

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Deb K. Pal

  • Lisa J. Strug

  • David A. Greenberg

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free