A large-scale genomic analysis has revealed some of the inner workings of the body clock, shedding new light on how it links to mental health and disease.
The study, published in Nature Communications, suggests that being genetically programmed to rise early may lead to greater well-being and a lower risk of schizophrenia and depression. However, despite much previous speculation, the results did not reveal any strong links to diseases such as diabetes or obesity.
The study was conducted by an international collaboration, led by the University of Exeter and Harvard-affiliated Massachusetts General Hospital (MGH) and funded primarily by the Medical Research Council of the U.K. It highlighted the key role of the retina in helping the body keep time. It also increased the number of areas of the genome known to influence whether someone is an early riser from 24 to 351.
Michael Weedon of the University of Exeter Medical School, who led the research, said, “This study highlights a large number of genes which can be studied in more detail to work out how different people can have different body clocks. The large number of people in our study means we have provided the strongest evidence to date that ‘night owls’ are at higher risk of mental health problems, such as schizophrenia and lower mental well-being, although further studies are needed to fully understand this link.”
The work was conducted in 250,000 U.S.-based research participants in 23andMe, a company that provides private genomic analyses, and 450,000 people in the U.K. Biobank study. All participants were asked if they were “morning people” or “evening people,” and their genomes were analyzed to look at genes they had in common that may influence their sleep patterns.
The researchers confirmed their results using information from wrist-worn activity trackers used by more than 85,000 individuals in the U.K. Biobank. This information showed that the genetic variants the researchers identified could shift a person’s natural waking time by up to 25 minutes — changing some people’s waking time from 8 a.m. to 8:25 a.m., for example. The researchers found that the genetic areas influenced sleep timing but not the quality or duration of sleep.
The genomic regions identified include those central to our body clocks, also referred to as circadian rhythms, as well as genes expressed in the brain and in retinal tissue. The body clock cycle is slightly longer than the 24-hour daily cycle. The retinal connection may help explain how the brain detects light to “reset” the body clock each day and align with the 24-hour cycle. Our body clocks are influenced by genes and lifestyle factors including diet, exposure to artificial light, and our jobs and activities. Our body clock affects a wide range of molecular processes, including hormone levels and core body temperature, as well as our waking and sleeping patterns.
Lead author Samuel E. Jones of the University of Exeter Medical School said, “The discovery of this fundamental body-clock mechanism in the brain recently won the Nobel Prize for medicine in 2017. However, we still know very little about whether or not your body clock influences your risk of disease. Our work indicates that part of the reason why some people are up with the lark while others are night owls is because of differences in both the way our brains react to external light signals and the normal functioning of our internal clocks. These small differences may have potentially significant effects on the ability of our body clocks to keep time effectively, potentially altering risk of both disease and mental health disorders.”
Co-lead author Jacqueline Lane of the MGH Department of Anesthesia added, “By understanding the genetics of sleep and activity timing in the general population, we also gain insights into potential avenues of therapy for individuals with more extreme conditions, such as those with advanced or delayed circadian rhythm disorders.”
Co-senior author Richa Saxena, MGH Anaesthesia and an associate professor of anaesthesia at Harvard Medical School, said, “This study highlights the power of teamwork and large-scale human genetics to reveal new aspects of the biology and health implications of our body clocks. The results will also allow researchers to explore more deeply how living in conflict with our individual internal time can lead to poorer health and may point to future individualized intervention strategies.”
