Genetics of Human Sleep Behavioral Phenotypes

High-accuracy determination of internal circadian time from a single blood sample

“…Moreover, the phase of entrainment of humans is not a stable trait; it rather depends on many internal and external factors. It has a genetic basis (11), is age-and sex-dependent (10), and depends on light exposure level (12,13) and on the season (12,14) as well as on the location within the time zone (10).…”

The Genetic Regulation of Human Sleep-Wake Rhythms and Patterns

“…Inherent genetic and biological tendencies are subject to external factors, which can be confounding. Some of these confounds include considerable variability in assessed phenotypes, overlapping psychological pathology, environmental factors like medication or other drugs, social and cultural influences, and school/work pressures, all of which make objective assessments of sleep in large populations difficult to obtain (Chong et al, 2015;Hsu et al, 2015;Veatch, Keenan, Gehrman, Malow, & Pack, 2017).…”

“…The first step in studying the genetics of these traits is to identify affected and unaffected individuals in families through rigorous phenotyping. Careful attention must be paid to extreme, yet normal (nongenetic), variation in sleep onset and duration, adherence to established thresholds (defined to select for extreme phenotypes), and environmental or psychological influences that interfere with the phenotype of interest (Hsu et al, 2015). Subjects are recruited either by referral from clinicians or by self-referral.…”

“…The relative conservation of genes across species underlies the fundamental importance of these pathways in regulating the critical physiological process of circadian regulation and sleep. Because these pathways exist in humans, the confirmation, posttranscriptional regulation, and fine-tuning of these molecular elements have been significantly impacted by human genetics and in particular forward genetic screens using human subjects with heritable sleep traits (which will be discussed in detail in the following text) (Hsu, Ptá cek, & Fu, 2015).…”

What time is it? A tale of three clocks, with implications for personalized medicine

“…Understanding the cause for extreme points or statistical outliers in a given dataset may reveal useful information about normal and abnormal physiology. For example, genetic variants in sleep timing were identified in patients with Advanced Sleep Wake Phase Disorder (ASWPD) and Delayed Sleep Wake Phase Disorder (DSWPD), in which there can be large differences between social and circadian time 19,20 …”