Research identifies genetic causes of poor sleep

Summary: An uncommon variant of the PDE11A gene impacts both quality and duration of sleep. Genetic regions linked to sleep quality are also associated with serotonin production. The study also reveals those with the same hip circumference and a higher waist circumference sleep less, although the effect is small.

Source: University of Exeter

The international collaboration, led by the University of Exeter and published in Nature Communications, has found 47 links between our genetic code and the quality, quantity, and timing of how we sleep. They include ten new genetic links with sleep duration and 26 with sleep quality.

The Medical Research Council-funded study looked at data from 85,670 participants of UK Biobank and 5,819 individuals from three other studies, who wore accelerometers – wrist-worn devices (similar to a Fitbit) which record activity levels continuously. They wore the accelerometers continuously for seven days, giving more detailed sleep data than previous studies, which have relied on people accurately reporting their own sleep habits.

Among the genomic regions uncovered is a gene called PDE11A. The research team discovered that an uncommon variant of this gene affects not only how long you sleep but your quality of sleep too. The gene has previously been identified as a possible drug target for the treatment of people with neuropsychiatric disorders associated with mood stability and social behaviors.

The study also found that among people with the same hip circumference, a higher waist circumference resulted in less time sleeping, although the effect was very small – around 4 seconds less sleep per 1cm waist increase in someone with the average hip circumference of around 100cm.

The team involved colleagues from the Center for Sleep and Circadian Neurobiology in Pennsylvania, Massachusetts General Hospital as well as the Netherlands, France, and Switzerland. They found that collectively, the genetic regions linked to sleep quality are also linked to the production of serotonin – a neurotransmitter associated with feelings of happiness and wellbeing. Serotonin is known to play a key role in sleep cycles and is theorized to help promote deeper and more restful sleep.

Senior author Dr. Andrew Wood, of the University of Exeter Medical School, said: “We know that getting enough sleep improves our health and wellbeing, yet we still know relatively little about the mechanisms in our bodies that influence how we sleep. Changes in sleep quality, quantity and timing are strongly associated with several human diseases such as diabetes and obesity, and psychiatric disorders.

This shows a woman sleeping on a sofa

The group also found further evidence that Restless Leg Syndrome is linked to poorer sleep from the genetic variants they found to be associated with sleep measures derived from the accelerometer data. The image is in the public domain.

Lead author Dr. Samuel Jones, of the University of Exeter Medical School, said: “This study identifies genetic variants influencing sleep traits, and will provide new insights into the molecular role of sleep in humans. It is part of an emerging body of work which could one day inform the development of new treatments to improve our sleep and our overall health.”

The group also found further evidence that Restless Leg Syndrome is linked to poorer sleep from the genetic variants they found to be associated with sleep measures derived from the accelerometer data.

The full paper is entitled ‘Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour’

About this neuroscience research article

Source:
University of Exeter
Media Contacts:
Louise Vennells – University of Exeter
Image Source:
The image is in the public domain.

Original Research: Open access
“Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour”. Samuel E. Jones, Vincent T. van Hees, Diego R. Mazzotti, Pedro Marques-Vidal, Séverine Sabia, Ashley van der Spek, Hassan S. Dashti, Jorgen Engmann, Desana Kocevska, Jessica Tyrrell, Robin N. Beaumont, Melvyn Hillsdon, Katherine S. Ruth, Marcus A. Tuke, Hanieh Yaghootkar, Seth A. Sharp, Yingjie Ji, Jamie W. Harrison, Rachel M. Freathy, Anna Murray, Annemarie I. Luik, Najaf Amin, Jacqueline M. Lane, Richa Saxena, Martin K. Rutter, Henning Tiemeier, Zoltán Kutalik, Meena Kumari, Timothy M. Frayling, Michael N. Weedon, Philip R. Gehrman & Andrew R. Wood. Nature Communications 10, 1–12 doi:10.1038/s41467-019-09576-1

Abstract

Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour

Sleep is an essential human function but its regulation is poorly understood. Using accelerometer data from 85,670 UK Biobank participants, we perform a genome-wide association study of 8 derived sleep traits representing sleep quality, quantity and timing, and validate our findings in 5,819 individuals. We identify 47 genetic associations at P < 5 × 10−8, of which 20 reach a stricter threshold of P < 8 × 10−10. These include 26 novel associations with measures of sleep quality and 10 with nocturnal sleep duration. The majority of identified variants associate with a single sleep trait, except for variants previously associated with restless legs syndrome. For sleep duration we identify a missense variant (p.Tyr727Cys) in PDE11A as the likely causal variant. As a group, sleep quality loci are enriched for serotonin processing genes. Although accelerometer-derived measures of sleep are imperfect and may be affected by restless legs syndrome, these findings provide new biological insights into sleep compared to previous efforts based on self-report sleep measures.

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