The Genetic Regulation of Human Sleep-Wake Rhythms and Patterns

Abstract The application of forward genetic approaches to heritable human sleep and circadian traits has greatly refined our understanding of these indispensable processes. Familial advanced sleep phase is a circadian condition where affected individuals awaken and sleep significantly earlier compared with unaffected family members but have otherwise normal sleep. Causative genetic variants have led to an in-depth appreciation of the pathways of posttranslational regulation for known circadian proteins to affect the timing of sleep-wake behavior. The homeostatic drive to sleep, which is defined as an increasing propensity to sleep after periods of wakefulness, is altered in natural short sleep subjects who require significantly shorter sleep than conventional sleepers. Investigations into this condition led to the recent identification of a novel sleep gene/mutation, providing the first insight into a pathway regulating sleep need. A better understanding of the molecular regulation of sleep will undoubtedly set the stage for improving therapies for sleep disturbances.