The genetics of sleep disorders.

Most sleep disorders result from complex interactions between genes and the environment. Modern molecular techniques are increasingly applied to determine the contribution of genes to sleep and its disorders. The genetic basis of circadian rhythms has been explored using Drosophila and rodent models. This culminated in the identification of the molecular basis of one autosomal dominant form of familial advanced sleep phase syndrome: mutations in the human period 2 gene. Genetic studies in an autosomal recessive canine model of narcolepsy and in gene-targeted mice have identified the hypothalamic hypocretin (orexin) neuropeptide system as a key target for human narcolepsy. In this case, animal models have provided important clues to a human disorder with complex genetics. The study of the role of genes in the obstructive sleep apnoea syndrome is likely to provide important clues to a phenotype associated with respiratory, cardiovascular, and metabolic dysfunction. This brief review will present the role of genetic factors in the obstructive sleep apnoea syndrome, restless leg syndrome, narcolepsy, and circadian rhythm disorders.