Genetic Markers of Individual Differences in Response to Sleep Loss

This chapter focuses on genotype-driven interindividual differences in phenotypic neurobehavioral responses to different types of sleep loss, including sleep restriction and total sleep deprivation. We highlight the utility of the candidate gene approach to further examine differential neurobehavioral vulnerability to sleep loss in humans, although the genome-wide association approach and other methods are also important for the investigation of biomarkers of such vulnerability. Notable genetic polymorphisms indicative of individual differences to sleep deprivation include those found in core circadian clock genes (BHLHE41/DEC2 and PER3), genes related to synaptic plasticity, cognitive development and functioning (BDNF and COMT), immune and clearance genes (AQP4, DQB1*0602, and TNFα), adenosine genes (ADA and ADORA2A), and dopaminergic genes (DRD2 and DAT). In addition to discussing the relevance of these polymorphisms to responses to sleep loss, we review the efficacy of several mitigation strategies and countermeasures for the neurobehavioral deficits induced by insufficient sleep, including banking sleep, recovery sleep, caffeine, and naps. The discovery of reliable genetic markers of differential resilience and vulnerability to sleep deprivation is essential to guide future research in sleep and circadian science regarding predictors, countermeasures, and treatments in applied settings.