A systems biology approach for uncovering the genetic landscape for multiple sleep-wake traits

The very complexity of sleep leads to the prediction that the underlying regulatory process will involve products of many interrelated genes. Thus, complex genetic and genomic approaches are likely to be powerful tools to probe components underlying the sleep–wake cycle and aid in understanding sleep physiology and regulation. Only recently have system genetics approaches been used to uncover the complex genetic landscape and gene networks that underlie multiple interrelated sleep traits. Aside from the recent advances in genetic tools, future sleep genetic studies are expected to benefit from new developments in genetic methodologies, such as systems genetics approaches discussed in detail in this review. Although still in the early stages of discovery, systems genetics approaches have identified novel genes involved in sleep. Future analyses of rich available data sets on multiple sleep–wake phenotypes, linked to genomic loci and gene expression profiles in multiple brain regions in segregating mouse populations, are expected to yield new insights into sleep–wake regulatory mechanisms, as well as sleep disorders, and for revealing new potential targets for pharmacological interventions. These new approaches have provided a previously underappreciated network view of the genetic regulation of sleep.