Identification of Novel Circadian Biomarkers
Condition: Circadian Rhythm Disorders
MeSH terms: Chronobiology Disorders
Study type: Observational

Summary: 
      Circadian clocks are not only found in discrete areas of the brain, but are found in
      virtually every organ in our bodies, including the heart, lungs and immune system.
      Disruptions in circadian clocks, or chronopathology, may underlie various forms of
      cardiovascular, pulmonary, and metabolic disorders. Over the past two decades, molecular
      geneticists have "cracked" the clock to reveal its core biochemical mechanisms evident in
      organisms from fruit flies to humans. These mechanistic insights have led to the discovery of
      links between clock function and an ever-expanding array of prevalent diseases, including
      heart, lung, metabolic and sleep disorders. Yet the prevalence of circadian disruption in
      these patient populations is unclear because current tests are not easily applied in clinical
      settings or have yet to be developed. Here the investigators exploit our newfound
      understanding of clock mechanisms and the development of new genomic technologies to identify
      novel complements of clock-regulated genes ("signatures") that will reveal the state of the
      internal biological clock. This approach will allow us to take a genomic snapshot of clock
      status from a single blood draw, substantially easing the diagnosis of these individuals with
      evidence of circadian disruption or misalignment, i.e., chronopathology.
    

Detailed description: 
      Circadian clocks are not only found in discrete areas of the brain, but are found in
      virtually every organ in our bodies, including the heart, lungs and immune system.
      Disruptions in circadian clocks, or chronopathology, may underlie various forms of
      cardiovascular, pulmonary, and metabolic disorders. Over the past two decades, molecular
      geneticists have "cracked" the clock to reveal its core biochemical mechanisms evident in
      organisms from fruit flies to humans. These mechanistic insights have led to the discovery of
      links between clock function and an ever-expanding array of prevalent diseases, including
      heart, lung, metabolic and sleep disorders. Yet the prevalence of circadian disruption in
      these patient populations is unclear because current tests are not easily applied in clinical
      settings or have yet to be developed. Perhaps the major limitation of these techniques is the
      need for serial sampling over extended periods of at least 24 hours and in some cases longer.
      The development of an assay from a single blood draw would represent a major step forward,
      facilitating assessments of circadian disruption in a range of diseases.

      An alternative strategy to existing assays is to use genomic microarrays to analyze circadian
      rhythms. Many studies in a number of organisms as well as multiple organs and tissues have
      found that substantial fractions of the genome (2-10%) are under robust circadian clock
      control. Importantly, these hundreds of rhythmic genes exhibit expression peaks at all times
      throughout the day, presumably reflecting their time-of-day specific functions. Using this as
      a foundation, Ueda and colleagues proposed an alternative strategy that would allow
      assessment of circadian time from a single blood draw allowing more routine assessments of
      circadian clock state. In brief, they identified the complement of rhythmic genes in livers
      of mice. They then selected a set of approximately 50 genes with unique peak times as
      "time-indicating genes." They then assessed the transcript levels of these time-indicating
      genes at a single time of day and found that they could accurately determine the time of day
      that the liver was taken based on the relative expression levels of the time-indicating
      genes. These studies provide proof-of-principle for the approach that we propose here.
      Establishing a molecular assay in humans for circadian rhythms from a single time point will
      allow us to identify circadian rhythm disorders, and to assess internal biological time to
      deliver therapies at their most efficacious time.
    

Observational model: Other
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        Healthy controls, age 18-60 with habitual sleep
      
Biospecimen description: 
      Blood, saliva and skin samples
    
Keywords: circadian; sleep