How should we be searching for genes for common epilepsy? A critique and a prescription.

Despite enormous data collection and analysis efforts, the genetic influences on common epilepsies remain mostly unknown. We propose that reasons for the lack of progress can be traced to three factors: (1) A reluctance to consider fine-grained phenotype definitions based on extensive and carefully collected clinical data; (2) the pursuit of genetic analysis methods that are popular but poorly conceived and are inadequate to the task of resolving the problems inherent in common disease studies; (3) preconceived ideas about the genetic mechanisms that cause epilepsy (which we have discussed elsewhere). We propose a paradigm for finding epilepsy-related loci and alleles that has proven successful in other common diseases.