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Largest-ever study identifies gene regions associated with sleep duration

March 07, 2019

A study led by investigators from Massachusetts General Hospital (MGH) and the University of Exeter Medical School has identified 76 new gene regions associated with sleep duration. The study by a team that recently reported finding gene sites associated with insomnia risk and chronotype - the tendency to be an early riser or a 'night owl' - has been published in Nature Communications.

"While we spend about a third of our life asleep, we have little knowledge of the specific genes and pathways that regulate the amount of sleep people get," says Hassan Saeed Dashti, PhD, RD, of the MGH Center for Genomic Medicine, co-lead author of the report. "Our study suggests that many of the genes important for sleep in animal models may also influence sleep in humans and opens the door to better understanding of the function and regulation of sleep."

It is well understood that regularly getting adequate sleep - 7 to 8 hours per night - is important to health, and both insufficient sleep - 6 or fewer hours - and excessive sleep - 9 hours or more - have been linked to significant health problems. Family studies have suggested that from 10 to 40 percent of variation in sleep duration may be inherited, and previous genetic studies have associated variants in two gene regions with sleep duration.

The current study, the largest of its kind to address sleep duration, analyzed genetic data from more than 446,000 participants in the U.K. Biobank who self-reported the amount of sleep they typically received. That genome-wide association study (GWAS) identified 78 gene regions - including the two previously identified - as associated with sleep duration. While carrying a single gene variant influenced the average amount of sleep by only a minute, participants carrying the largest number of duration-increasing variants reported an average of 22 more minutes of sleep, compared with those with the fewest, which is comparable to other well-recognized factors that influence sleep duration.

To confirm the accuracy of findings based on self-reported sleep duration, the researchers tested the 78 duration-associated variants in a subgroup of participants who had worn motion-detecting devices called accelerometers for up to a week. Not only were those gene regions supported by objective measurement of sleep duration, but this analysis was also able to associate duration-related variants with factors such as sleep efficiency, instances of waking up during the night and daytime inactivity.

Only a few of the gene regions identified in this study overlap with those identified in the group's previous studies of insomnia and chronotype. The sites identified in this study showed consistent effects with a previous GWAS of more than 47,000 adults but limited consistency with another GWAS of sleep duration among more than 10,500 children and adolescents, which supports research suggesting that the genetics of sleep duration may be different in children than in adults.

Since both shorter- and longer-than-average sleep duration have been associated with health problems, the team conducted separate GWASs for participants who reported short or long sleep duration. Those studies identified additional genes not identified in the larger group analysis that contributed to either longer or shorter sleep duration. The researchers also found shared genetic links between both short and long sleep duration and factors such as higher levels of body fat, depression symptoms and fewer years of schooling, implying negative effects from both too little and too much sleep. In addition, short sleep duration was genetically linked with traits such as insomnia and smoking, while long-duration variants were linked with schizophrenia, type 2 diabetes and coronary artery disease.
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Co-lead author Samuel Jones, PhD, of the University of Exeter Medical School, says the new study complements the team's recent publications. "Finding 78 areas of the genome that influence habitual sleep duration represents a huge leap forward in our understanding of the mechanisms behind why some people need more sleep than others. As part of a wider body of work, our discoveries have the potential to aid the discovery of new treatments for sleep and sleep-related disorders."

Co-senior and corresponding author Richa Saxena, PhD, MGH Center for Genomic Medicine, adds, "While follow-up studies are required to clarify the functional impact of these variants, the associated genes are known to play a role in brain development and in the transmission of signals between neurons. These findings suggest themes for future investigations of the sleep-wake control centers of the brain that will help us tease apart mechanisms of disordered sleep and help understand each person's natural set point for refreshing sleep." Saxena is an associate professor of Anesthesia at Harvard Medical School.

Andrew Wood, PhD, of the University of Exeter Medical School is also co-lead author of the Nature Communications paper, and Michael Weedon, PhD, University of Exeter, and Martin Rutter, MD, MRCP, University of Manchester, are co-senior authors. Support for the study includes National Institutes of Health grants R01 DK107859 and R01 DK102696, and an MGH Research Scholar Award.

The University of Exeter Medical School is improving the health of the South West and beyond, through the development of high-quality graduates and world-leading research that has international impact. As part of a Russell Group university, we combine this world-class research with very high levels of student satisfaction. Part of the University of Exeter's College for Medicine and Health, the University of Exeter Medical School's Medicine programme is ranked 5th in the Guardian Guide 2018, while Medical Imaging is ranked 2nd, in the Complete University Guide 2018, under Radiography. Exeter has over 19,000 students and is ranked 12th in The Times and The Sunday Times Good University Guide 2018. In the 2014 Research Excellence Framework (REF), the University ranked 16th nationally, with 98 percent of its research rated as being of international quality. Exeter's Clinical Medicine research was ranked 3rd in the country, based on research outputs that were rated world-leading. Public Health, Health Services and Primary Care research also ranked in the top ten, in joint 9th for research outputs rated world-leading or internationally excellent.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $925 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2018 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."

Massachusetts General Hospital

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