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      Association of accelerometer-derived sleep measures with lifetime psychiatric diagnoses: A cross-sectional study of 89,205 participants from the UK Biobank

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Sleep problems are both symptoms of and modifiable risk factors for many psychiatric disorders. Wrist-worn accelerometers enable objective measurement of sleep at scale. Here, we aimed to examine the association of accelerometer-derived sleep measures with psychiatric diagnoses and polygenic risk scores in a large community-based cohort.

          Methods and findings

          In this post hoc cross-sectional analysis of the UK Biobank cohort, 10 interpretable sleep measures—bedtime, wake-up time, sleep duration, wake after sleep onset, sleep efficiency, number of awakenings, duration of longest sleep bout, number of naps, and variability in bedtime and sleep duration—were derived from 7-day accelerometry recordings across 89,205 participants (aged 43 to 79, 56% female, 97% self-reported white) taken between 2013 and 2015. These measures were examined for association with lifetime inpatient diagnoses of major depressive disorder, anxiety disorders, bipolar disorder/mania, and schizophrenia spectrum disorders from any time before the date of accelerometry, as well as polygenic risk scores for major depression, bipolar disorder, and schizophrenia. Covariates consisted of age and season at the time of the accelerometry recording, sex, Townsend deprivation index (an indicator of socioeconomic status), and the top 10 genotype principal components. We found that sleep pattern differences were ubiquitous across diagnoses: each diagnosis was associated with a median of 8.5 of the 10 accelerometer-derived sleep measures, with measures of sleep quality (for instance, sleep efficiency) generally more affected than mere sleep duration. Effect sizes were generally small: for instance, the largest magnitude effect size across the 4 diagnoses was β = −0.11 (95% confidence interval −0.13 to −0.10, p = 3 × 10 −56, FDR = 6 × 10 −55) for the association between lifetime inpatient major depressive disorder diagnosis and sleep efficiency. Associations largely replicated across ancestries and sexes, and accelerometry-derived measures were concordant with self-reported sleep properties. Limitations include the use of accelerometer-based sleep measurement and the time lag between psychiatric diagnoses and accelerometry.

          Conclusions

          In this study, we observed that sleep pattern differences are a transdiagnostic feature of individuals with lifetime mental illness, suggesting that they should be considered regardless of diagnosis. Accelerometry provides a scalable way to objectively measure sleep properties in psychiatric clinical research and practice, even across tens of thousands of individuals.

          Abstract

          In a cross-sectional study, Michael Wainberg and colleagues investigate the association between accelerometer-derived sleep measures and lifetime psychiatric diagnoses.

          Author summary

          Why was this study done?
          • Sleep problems are both symptoms of and risk factors for many mental health conditions.

          • This study aimed to determine how objectively measured sleep differs among individuals with lifetime psychiatric diagnoses.

          What did the researchers do and find?
          • This cohort study of 89,205 individuals from the UK Biobank analyzed 10 accelerometer-derived sleep measures.

          • The study found a rich suite of associations with lifetime diagnoses of psychopathology and psychiatric polygenic risk scores, though effect sizes were generally small.

          What do these findings mean?
          • Sleep pattern differences are the norm among patients with lifetime psychiatric illness.

          • Accelerometry provides a scalable way to objectively measure such differences in psychiatric research and practice.

          • Limitations include the use of accelerometer-based sleep measurement and the time lag between psychiatric diagnoses and accelerometry.

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          Most cited references59

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

            Summary Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding Bill & Melinda Gates Foundation.
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              Second-generation PLINK: rising to the challenge of larger and richer datasets

              PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for even faster and more scalable implementations of key functions. In addition, GWAS and population-genetic data now frequently contain probabilistic calls, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format. To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, O(sqrt(n))-time/constant-space Hardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. This will be followed by PLINK 2.0, which will introduce (a) a new data format capable of efficiently representing probabilities, phase, and multiallelic variants, and (b) extensions of many functions to account for the new types of information. The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: SupervisionRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                plos
                PLoS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                12 October 2021
                October 2021
                : 18
                : 10
                : e1003782
                Affiliations
                [1 ] Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, Canada
                [2 ] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
                [3 ] University of Exeter Medical School, Exeter, United Kingdom
                [4 ] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada
                [5 ] Institute of Medical Sciences, University of Toronto, Toronto, Canada
                [6 ] Department of Psychiatry, University of Toronto, Toronto, Canada
                [7 ] Department of Physiology, University of Toronto, Toronto, Canada
                [8 ] Biostatistics Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
                [9 ] Department of Genetics, Stanford University, Stanford, California, United States of America
                [10 ] Sunnybrook Health Sciences Centre, Toronto, Canada
                [11 ] Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada
                [12 ] Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
                [13 ] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America
                [14 ] Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
                Harvard Medical School, UNITED STATES
                Author notes

                I have read the journal’s policy and the authors of this manuscript have the following competing interests: M.A.R. is on the SAB of 54Gene, Related Sciences and scientific founder of Broadwing Bio and has advised BioMarin, Third Rock Ventures and MazeTx; the remaining authors declare no competing interests.

                Author information
                https://orcid.org/0000-0001-6061-0239
                https://orcid.org/0000-0003-0153-922X
                https://orcid.org/0000-0001-8224-1307
                https://orcid.org/0000-0001-8055-860X
                https://orcid.org/0000-0003-1831-9848
                https://orcid.org/0000-0003-1457-9925
                https://orcid.org/0000-0003-2179-1553
                https://orcid.org/0000-0002-5302-6429
                https://orcid.org/0000-0002-1007-9061
                Article
                PMEDICINE-D-21-02038
                10.1371/journal.pmed.1003782
                8509859
                34637446
                9e962161-e94b-45e7-bbe2-3f8bb350bdcc
                © 2021 Wainberg et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 4 May 2021
                : 25 August 2021
                Page count
                Figures: 1, Tables: 4, Pages: 18
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100001201, kavli foundation;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004089, krembil foundation;
                Award Recipient :
                Funded by: camh discovery fund
                Award Recipient :
                Funded by: mclaughlin foundation
                Award Recipient :
                Funded by: nserc
                Award ID: RGPIN-2020-05834
                Award Recipient :
                Funded by: nserc
                Award ID: DGECR-2020-00048
                Award Recipient :
                Funded by: cihr
                Award ID: NGN-171423
                Award Recipient :
                Funded by: michael and sonja koerner foundation new scientist program
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004089, krembil foundation;
                Award Recipient :
                Funded by: camh discovery fund
                Award Recipient :
                Funded by: mclaughlin foundation
                Award Recipient :
                The authors acknowledge Milos Milic for data curation assistance. MW and SJT acknowledge support from the Kavli Foundation, Krembil Foundation, CAMH Discovery Fund, the McLaughlin Foundation, NSERC (RGPIN-2020-05834 and DGECR-2020-00048) and CIHR (NGN-171423). DF is supported by the Michael and Sonja Koerner Foundation New Scientist Program, Krembil Foundation, CAMH Discovery Fund, and the McLaughlin Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research was conducted under the auspices of UK Biobank application 61530, “Multimodal subtyping of mental illness across the adult lifespan through integration of multi-scale whole-person phenotypes”.
                Categories
                Research Article
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Sleep
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Mood Disorders
                Depression
                Medicine and Health Sciences
                Health Care
                Patients
                Inpatients
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Schizophrenia
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Mood Disorders
                Bipolar Disorder
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Neuropsychiatric Disorders
                Anxiety Disorders
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Neuroses
                Anxiety Disorders
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Custom metadata
                De-identified data for the 10 accelerometer-derived sleep measures used in the study are available through the UK Biobank. The data are available to researchers through a procedure described at http://www.ukbiobank.ac.uk/using-the-resource/.

                Medicine
                Medicine

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