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

• Published in: Nature communications Vol. 10; no. 1; pp. 1585 - 12
• Main Authors: Jones, Samuel E., van Hees, Vincent T., Mazzotti, Diego R., Marques-Vidal, Pedro, Sabia, Séverine, van der Spek, Ashley, Dashti, Hassan S., Engmann, Jorgen, Kocevska, Desana, Tyrrell, Jessica, Beaumont, Robin N., Hillsdon, Melvyn, Ruth, Katherine S., Tuke, Marcus A., Yaghootkar, Hanieh, Sharp, Seth A., Ji, Yingjie, Harrison, Jamie W., Freathy, Rachel M., Murray, Anna, Luik, Annemarie I., Amin, Najaf, Lane, Jacqueline M., Saxena, Richa, Rutter, Martin K., Tiemeier, Henning, Kutalik, Zoltán, Kumari, Meena, Frayling, Timothy M., Weedon, Michael N., Gehrman, Philip R., Wood, Andrew R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.04.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 45/43; 631/208/1515; 631/208/205/2138; 631/378/1385/2640; 631/378/1385/519; Accelerometers; Accelerometry - methods; Circadian Rhythm; Genome-wide association studies; Genomes; Human behavior; Humanities and Social Sciences; Humans; Leg; Legs; multidisciplinary; Nocturnal; Polymorphism, Single Nucleotide; Polysomnography - methods; Restless legs syndrome; Science; Science (multidisciplinary); Serotonin; Serotonin - genetics; Serotonin - metabolism; Sleep; Sleep - genetics; Sleep deprivation; Sleep Wake Disorders - diagnosis; Sleep Wake Disorders - genetics; Waist-Hip Ratio
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09576-1

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. Quality, quantity and timing of sleep are important factors for overall human health. Here, the authors perform GWAS for sleep traits estimated using wearable accelerometers and identify 47 genetic associations, including 26 novel associations for measures of sleep quality and 10 for nocturnal sleep duration.