Dashti, Hassan S., Jones, Samuel E., Wood, Andrew R., Lane, Jacqueline M., Van Hees, Vincent T., Wang, Heming, Rhodes, Jessica A., Song, Yanwei, Patel, Krunal, Anderson, Simon G., Beaumont, Robin N., Bechtold, David A., Bowden, Jack, Cade, Brian E., Garaulet, Marta, Kyle, Simon D., Little, Max A., Loudon, Andrew S., Luik, Annemarie I., Scheer, Frank A. J. L., Spiegelhalder, Kai, Tyrrell, Jessica, Gottlieb, Daniel J., Tiemeier, Henning, Ray, David W., Purcell, Shaun M., Frayling, Timothy M., Redline, Susan, Lawlor, Deborah A., Rutter, Martin K., Weedon, Michael N. and Saxena, Richa (2019). Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates. Nature Communications, 10 (1),
Abstract
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.
Publication DOI: | https://doi.org/10.1038/s41467-019-08917-4 |
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Divisions: | College of Engineering & Physical Sciences > Systems analytics research institute (SARI) |
Additional Information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Uncontrolled Keywords: | Accelerometry,Adult,Aged,European Continental Ancestry Group,Female,Genetic Loci,Genome-Wide Association Study,Humans,Linkage Disequilibrium,Male,Middle Aged,Polymorphism, Single Nucleotide,Schizophrenia/genetics,Self Report,Sleep/genetics,United Kingdom,General Physics and Astronomy,General Chemistry,General Biochemistry,Genetics and Molecular Biology |
Publication ISSN: | 2041-1723 |
Last Modified: | 31 Oct 2024 08:20 |
Date Deposited: | 13 Mar 2019 12:52 |
Full Text Link: | |
Related URLs: |
http://www.natu ... 467-019-08917-4
(Publisher URL) http://www.scop ... tnerID=8YFLogxK (Scopus URL) |
PURE Output Type: | Article |
Published Date: | 2019-03-07 |
Accepted Date: | 2019-01-31 |
Authors: |
Dashti, Hassan S.
Jones, Samuel E. Wood, Andrew R. Lane, Jacqueline M. Van Hees, Vincent T. Wang, Heming Rhodes, Jessica A. Song, Yanwei Patel, Krunal Anderson, Simon G. Beaumont, Robin N. Bechtold, David A. Bowden, Jack Cade, Brian E. Garaulet, Marta Kyle, Simon D. Little, Max A. ( 0000-0002-1507-3822) Loudon, Andrew S. Luik, Annemarie I. Scheer, Frank A. J. L. Spiegelhalder, Kai Tyrrell, Jessica Gottlieb, Daniel J. Tiemeier, Henning Ray, David W. Purcell, Shaun M. Frayling, Timothy M. Redline, Susan Lawlor, Deborah A. Rutter, Martin K. Weedon, Michael N. Saxena, Richa |