Genetic basis of sleep disorders

Abstract

Sleep as all other complex phenotypes is regulated by genes and environment. Although many sleep disorders run in families, only few have an established genetic basis but their number is increasing. Recent progress in molecular genetics has led to the discovery of the orexin deficiency in narcolepsy and indicates that similar approaches are needed in order to understand the molecular basis of other sleep disorders. Among the best candidates are common sleep disorders such as sleep apnoea, sleepwalking, restless-legs syndrome and primary nocturnal enuresis. Most sleep disorders are complex and many genes, environment and gene-environment interactions might contribute to the final phenotype. Even at the genetic level, these disorders are still too complex for detailed analysis and sequential approaches, taking into account different aspects of the disorder, are needed. Sleep apnoea is the best example for which morphological, chemosensitivity, arousability and many other simple phenotypes should be considered one by one for a thorough genetic dissection. Here we review key sleep disorders with strong evidence for a major genetic contribution. We believe that molecular genetics constitute our best hope for future development of appropriate pharmacogenetically-based treatments.