Journal Article

Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

Song, Yanwei, Bowden, Jack, Weedon, Michael N., Patel, Krunal, Bechtold, David A., Garaulet, Marta, Rutter, Martin K., Rhodes, Jessica A., Scheer, Frank A. J. L., Redline, Susan, Tyrrell, Jessica, Beaumont, Robin N., Loudon, Andrew S., Anderson, Simon G., van Hees, Vincent T., Frayling, Timothy M., Spiegelhalder, Kai, Wood, Andrew R., Purcell, Shaun M., Lawlor, Deborah A., Jones, Samuel E., Gottlieb, Daniel J., Ray, David W., Little, Max A., Luik, Annemarie I., Kyle, Simon D., Lane, Jacqueline M., Saxena, Richa, Dashti, Hassan S., Wang, Heming, Cade, Brian E., Tiemeier, Henning

2019

Overview

Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration ( p  < 5 × 10 −8 ; 43 loci at p  < 6 × 10 −9 ). Replication is observed for PAX8 , VRK2 , and FBXL12/UBL5/PIN1 loci in the CHARGE study ( n  = 47,180; p  < 6.3 × 10 −4 ), and 55 signals show sign-concordant effects. The 78 loci further associate with accelerometer-derived sleep duration, daytime inactivity, sleep efficiency and number of sleep bouts in secondary analysis ( n  = 85,499). Loci are enriched for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission and plasticity, among others. Genetic correlation indicates shared links with anthropometric, cognitive, metabolic, and psychiatric traits and two-sample Mendelian randomization highlights a bidirectional causal link with schizophrenia. This work provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways. Sleep is essential for homeostasis and insufficient or excessive sleep are associated with adverse outcomes. Here, the authors perform GWAS for self-reported habitual sleep duration in adults, supported by accelerometer-derived measures, and identify genetic correlation with psychiatric and metabolic traits

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38 / 45/43 / 631/208/205/2138 / 631/378/2583 / 631/443/376 / 692/499 / Accelerometers / Accelerometry / Adult / Adults / Aged / Alertness / Anthropometry / Association analysis / Cognitive ability / Dopamine / Female / Gene loci / Genetic diversity / Genetic Loci / Genome-wide association studies / Genome-Wide Association Study / Genomes / Humanities and Social Sciences / Humans / Linkage Disequilibrium / Male / Mental disorders / Middle Aged / multidisciplinary / Neostriatum / Neurotransmission / Pax8 protein / Pin1 protein / Polymorphism, Single Nucleotide / Schizophrenia / Schizophrenia - genetics / Schizophrenia - physiopathology / Science / Science (multidisciplinary) / Secondary analysis / Self Report / Sleep / Sleep - genetics / Sleep - physiology / Synaptic plasticity / United Kingdom / White People