Genetics of Chronotype and Circadian Rhythm Disorders

Circadian rhythms are important biological processes that are essential to human health and well-being. These rhythms are generated by the internal “body clock” and regulate the sleep-wake cycle and numerous physiological processes. Mutations (i.e., changes in circadian genes) from one generation to the next including underlying genetic issues which may result in one’s inability to receive or process environmental cues can affect the clock’s timing. However, circadian rhythm disruption may also be related to external factors and an individual’s behavior as a result of their sleep timing (chronotype) or due to activities such as trans-meridian travel and shift-work that puts sleep schedules out of sync with daylight exposure. Dysregulation of the body’s internal circadian timekeeping mechanism is an established risk factor for circadian rhythm sleep-wake disorders (CRSWD). This dysregulation is common in modern society and is associated with a number of highly prevalent population diseases including CRSWD. CRSWDs involve a disruption in the timing of physiological processes, including sleep and wake timing. There is evidence of genetic variation playing a role in chronotype, with circadian, behavioral and photo-transduction pathways implicated using large scale GWAS, providing opportunities to better understand the causes and consequences of circadian rhythm disturbances on human physiology. As well, both Advanced and Delayed Sleep Wake Phase Disorders have been linked to rare genetic variation in circadian clock genes in families. In this chapter, we will focus on the genetics of chronotype and CRSWDs in humans, additionally looking at the role of chronomedicine in providing precision medicine for the treatment of CRSWDs. Thus, this chapter seeks to expand our knowledge of the genetic basis of chronotype and CRSWDs.