GWAS in 446,118 European adults identifies 78 genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates
Open accessPreprint — published as 10.1038/s41467-019-08917-4
Abstract
Sleep is an essential homeostatically-regulated state of decreased activity and alertness conserved across animal species, and both short and long sleep duration associate with chronic disease and all-cause mortality 1,2 . Defining genetic contributions to sleep duration could point to regulatory mechanisms and clarify causal disease relationships. Through genome-wide association analyses in 446,118 participants of European ancestry from the UK Biobank, we discover 78 loci for self-reported sleep duration that further impact accelerometer-derived measures of sleep duration, daytime inactivity duration, sleep efficiency and number of sleep bouts in a subgroup ( n =85,499) with up to 7-day accelerometry. Associations are enriched for genes expressed in several brain regions, and for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission, catecholamine production, synaptic plasticity, and unsaturated fatty acid metabolism. Genetic correlation analysis indicates shared biological links between sleep duration and psychiatric, cognitive, anthropometric and metabolic traits and Mendelian randomization highlights a causal link of longer sleep with schizophrenia.
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We found concordance for loci previously reported using UK Biobank data for overall and moderate intensity activity, sleep duration, and sedentary time.
“We found concordance for loci previously reported using UK Biobank data for overall (near PML) and moderate intensity activity8 (near LINC02210-CRHR1, and SYT4), sleep duration12,19,23,24 (near PUM1, CHCHD5, SAMMSON, BTBD9-AS1, LRP12, EBLN3P, BSX, KCNH5, PRKCB, and RPGRIP1L), and sedentary time (near LINC01930 and LY6H) (Supplementary Data 3).”
From GWAS identifies 14 loci for device-measured physical activity and sleep duration (2018) · cites this paper as [24]
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Genetics of Circadian and Sleep Measures in Adults: Implications for Sleep Medicine
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Pott, J., Kheirkhah, A., Gådin, J. R., Kleber, M. E., Delgado, G. E., Kirsten, H., Forer, L., Hauck, S. M., Burkhardt, R., Scharnagl, H., et al. (2024) · Biology of Sex Differences · doi:10.1186/s13293-024-00602-6 · Cited by 5 · see citing works
Richmond, R. C., Anderson, E. L., Dashti, H. S., Jones, S. E., Lane, J. M., Strand, L. B., Brumpton, B. M., Rutter, M. K., Wood, A. R., Relton, C. L., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/457572 · Cited by 4 · see citing works
“Genetic variants robustly associated with chronotype, sleep duration and insomnia symptoms have recently been identified in large genome wide association studies (GWAS) with sample sizes of ~50,000 to >1 million participants (15–23).”
BackgroundMethodInfluentialSelf-citationWang, H.-M., Lane, J., Jones, S., et al. (2018) · bioRxiv · doi:10.1101/454561 · Cited by 3
Self-citationThe comprehensive genetic architecture of brain white matter
Zhao, B.-X., Li, T., Yang, Y., et al. (2020) · bioRxiv · doi:10.1101/2020.05.23.112409 · Cited by 2
Noordam, R., Bos, M. M., Wang, H., Winkler, T. W., Bentley, A. R., Kilpeläinen, T. O., de Vries, P. S., Sung, Y. J., Schwander, K., Cade, B. E., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/559393 · Cited by 1 · see citing works
Self-citationDifferences in Genetic Liability for Insomnia and Hypersomnia in Bipolar Disorder SubtypesPreprint
Lewis, K. S., Richards, A. L., Leonenko, G., Jones, S. E., Jones, H. J., Gordon‐Smith, K., Forty, L., Escott‐Price, V., Owen, M. J., Weedon, M. N., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/569376
Self-citation
- Authors
- Dashti, H. S., Jones, S. E., Wood, A. R., Lane, J. M., van Hees, V. T., Wang, H., Rhodes, J. A., Song, Y., Patel, K., Anderson, S. G., Beaumont, R., Bechtold, D. A., Bowden, J., Cade, B. E., Garaulet, M., Kyle, S. D., Little, M. A., Loudon, A. S., Luik, A. I., Scheer, F. A., Spiegelhalder, K., Tyrrell, J., Gottlieb, D. J., Tiemeier, H., Ray, D. W., Purcell, S. M., Frayling, T. M., Redline, S., Lawlor, D. A., Rutter, M. K., Weedon, M. N., & Saxena, R.
- Affiliations
- Broad Institute (US)
- University of Exeter (GB)
- Northeastern University (US)
- University of Manchester (GB)
- University of Bristol (GB)
- Instituto Murciano de Investigación Biosanitaria (ES)
- University of Oxford (GB)
- Aston University (GB)
- University of Freiburg (DE)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Manchester Academic Health Science Centre (GB)
- Corresponding author
- Saxena, Richa
- ORCID
- Dashti, Hassan S
- Jones, Samuel E
- Wood, Andrew R
- Lane, Jacqueline M
- Wang, Heming
- Rhodes, Jessica A
- Song, Yanwei
- Anderson, Simon G
- Beaumont, Robin
- Bechtold, David A
- Bowden, Jack
- Cade, Brian E
- Garaulet, Marta
- Kyle, Simon D
- Little, Max A
- Loudon, Andrew S
- Luik, Annemarie I
- Scheer, Frank AJL
- Spiegelhalder, Kai
- Tyrrell, Jessica
- Gottlieb, Daniel J
- Tiemeier, Henning
- Ray, David W
- Purcell, Shaun M
- Frayling, Timothy M
- Redline, Susan
- Rutter, Martin K
- Weedon, Michael N
- Saxena, Richa
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2018-04-19
- Volume
- 10
- Issue
- 1
- Pages
- 1100-1100
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6405943
- OpenAlex
- W2912670585
- Cited by
- 614
- References
- 0
- Citations by year
- 2026: 71 · 2025: 91 · 2024: 113 · 2023: 85 · 2022: 101 · 2021: 58 · 2020: 62 · 2019: 27 · 2018: 6
- FWCI
- 72.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Aston Publications Explorer (Aston University) (acceptedVersion, other-oa)
- Open Research Exeter (University of Exeter) (acceptedVersion, cc-by)
- Explore Bristol Research (submittedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion, cc-by)
- Funders
- American Thoracic Society (K01-HL135405)
- Wellcome Trust (104150/Z/14/Z, 107849, 107851/Z/15/Z, 107849/Z/15/Z), /Z/15/Z, 104150, WT097835MF, 323195)
- National Institute for Health and Care Research (NF-SI-0611-10196, CL-2012-06-001)
- Diabetes Research and Wellness Foundation
- University of Manchester
- Novo Nordisk
- National Institutes of Health (5k01hl135405-04, NIH-R01, N01-HC 25195, K01-HL135405)
- Medical Research Council (MC_UU_00011/6, MR/M005070/1, MR/P012167/1, MR/P023576/2, WT097835MF, MC_UU_00011/2)
- National Heart, Lung, and Blood Institute (R01HL113338, K01-HL135405-01, U01HL053941, N01‐HC25195, K01-HL135405, HL113338, R35HL135818, N02- HL-64278, R35-HL135818-01, HL135818, K01HL136884, NIH R01, T32HL007901)
- National Institute of Mental Health (R03MH108908)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK105072, N01-HC-25195, NIDDK R01DK105072, R01DK102696, NIH R01, F32DK102323, R01DK107859)
- FP7 Ideas: European Research Council (323195)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- sleep duration, genetic loci, self-reported sleep, accelerometer-measured sleep, sleep efficiency, dopamine binding, synaptic transmission, genetic correlation, schizophrenia, Mendelian randomization, European ancestry
- MeSH terms
- Adult, Aged, Female, United Kingdom, Humans, Male, Middle Aged, Schizophrenia, Sleep, Linkage Disequilibrium, Polymorphism, Single Nucleotide, White People, Genome-Wide Association Study, Genetic Loci, Self Report, Accelerometry
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