The search for circadian clock components in humans: new perspectives for association studies

Abstract

Individual circadian clocks entrain differently to environmental cycles (zeitgebers, e.g., light and darkness), earlier or later within the day, leading to different chronotypes. In human populations, the distribution of chronotypes forms a bell-shaped curve, with the extreme early and late types -larks and owls, respectively -at its ends. Human chronotype, which can be assessed by the timing of an individual's sleep-wake cycle, is partly influenced by genetic factors -known from animal experimentation. Here, we review population genetic studies which have used a questionnaire probing individual daily timing preference for associations with polymorphisms in clock genes. We discuss their inherent limitations and suggest an alternative approach combining a short questionnaire (Munich ChronoType Questionnaire, MCTQ), which assesses chronotype in a quantitative manner, with a genome-wide analysis (GWA). The advantages of these methods in comparison to assessing time-of-day preferences and single nucleotide polymorphism genotyping are discussed. In the future, global studies of chronotype using the MCTQ and GWA may also contribute to understanding the influence of seasons, latitude (e.g., different photoperiods), and climate on allele frequencies and chronotype distribution in different populations.

Heritable circadian period length in a wild bird population

“…Estimated h 2 differed between 0.17 and 0.78, respectively, and t and phase under LD cycles were uncorrelated (Shimizu & Masaki 1997). The findings of selectable variation in a clock trait converge with circumstantial evidence for adaptive adjustment of circadian systems, inferred from latitudinal clines in clock properties and gene variants (Daan & Aschoff 1982;Pittendrigh & Takamura 1989;Price & Boag 1993;Decoursey 2004;Johnsen et al 2007;Allebrandt & Roenneberg 2008;Kyriacou et al 2008). Such microevolutionary adjustments could counteract possible constraints on flexibility that are thought to be imposed by circadian clocks (Kronfeld-Schor & Dayan 2003).…”

“…Individuals can hence be classified into 'chronotypes', depending on whether they are active relatively early or late in the day (Duffy et al 2001;Koukkari & Sothern 2006;Allebrandt & Roenneberg 2008). In many species, these individual differences in chronotype are related to free-running period length t (Duffy et al 2001;Allebrandt & Roenneberg 2008;Brown et al 2008;von Schantz 2008). Under LD cycles, individuals with shorter t tend to be active earlier in the day and to display more or longer lasting activity than those with longer t (Aschoff & Wever 1966;Fleury et al 2000;Brown et al 2008).…”

Obesity and shift work: chronobiological aspects

“…The circadian clock controls physiology from gene expression to complex behaviours (for example, sleep and performance). This internal control is synchronised to the exogenous environment through signals, such as transient night and day cycles, where light is captured by retinal and transduced to the SCN via collaterals of the optic nerve where they synchronise the circa-daily rhythm produced by SCN neurons to exactly 24 h. Via its rhythmic outputs, the SCN coordinates all the cellular circadian clocks, including clocks from adipose tissue, to adapt physiology to the Earth's rotation (29) . Circadian molecular clocks driven by autoregulatory transcription -translation feedback loops consist of a pair of activator proteins, CLOCK and BMAL-1, in mammals that induce the transcription of a pair of repressor genes Per and Cry, additionally regulated by modifiers (30) .…”

Cukrzyca w społeczeństwie 24/7. Związek między pracą zmianową a zaburzeniami metabolicznymi

“…suprachiasmatic nucleus) w podwzgórzu. SCN, znajdujące się ponad skrzyżowa-niem nerwów wzrokowych, mają za zadanie koordynowanie innych zegarów biologicznych, na przykład znajdujących się w tkankach metabolicznie czynnych, takich jak tkanka tłuszczowa [18,22,23]. Aktywność tego centralnego zegara biologicznego regulowana jest przede wszystkim światłem.…”