Evaluating candidate genes in common epilepsies and the nature of evidence
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Open Access
Abstract
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.Keywords
This publication has 45 references indexed in Scilit:
- Linkage and association analysis of CACNG3 in childhood absence epilepsyEuropean Journal of Human Genetics, 2007
- Heterogeneity at the JME 6p11–12 Locus: Absence of Mutations in the EFHC1 Gene in Linked Dutch FamiliesEpilepsia, 2006
- Can We Increase the Likelihood of Success for Future Association Studies in Epilepsy?Epilepsia, 2006
- A common variant associated with prostate cancer in European and African populationsNature Genetics, 2006
- Using Linkage Genome Scans to Improve Power of Association in Genome ScansThe American Journal of Human Genetics, 2006
- A locus for generalized tonic-clonic seizure susceptibility maps to chromosome 10q25-q26Annals of Neurology, 2005
- BRD2 (RING3) Is a Probable Major Susceptibility Gene for Common Juvenile Myoclonic EpilepsyThe American Journal of Human Genetics, 2003
- Reproducibility and Complications in Gene Searches: Linkage on Chromosome 6, Heterogeneity, Association, and Maternal Inheritance in Juvenile Myoclonic EpilepsyThe American Journal of Human Genetics, 2000
- Autosomal dominant rolandic epilepsy and speech dyspraxia: A new syndrome with anticipationAnnals of Neurology, 1995
- Genetics of autoimmune thyroid disease: lack of evidence for linkage to HLA within familiesThe Journal of Clinical Endocrinology & Metabolism, 1992