Sleep deficiency, poor sleep and night shift work increase risk of cardiovascular disease, type 2 diabetes, obesity, mood disorders and all cause mortality. Sleep disorders themselves pose a large public health and economic burden. Although sleep is a fundamental behavior with a significant genetic contribution, the genetic basis of variability in sleep regulation in the human population and shared biological pathways with chronic disease is almost completely unknown. Sleep duration, timing and quality are heritable, providing opportunities to identify underlying genes and biological pathways. However, sleep phenotypes also depend on social and environmental factors and disease conditions, requiring large datasets and careful consideration of covariates to detect genetic effects. We hypothesize that meta-analysis of genome-wide association studies (GWAS) using existing large-scale publicly available population-based datasets and enhanced statistical methods for admixture association and covariate modeling will identify new genes and biological pathways important for sleep regulation. In order to test this hypothesis, we propose the following specific aims: 1) To harmonize self-reported sleep duration, timing and quality phenotypes across publicly available datasets, and 2) To identify genetic variants associated with heritable sleep traits by performing GWAS and meta-analyses in subjects of European and African American (AA) ancestry. Identifying genes for sleep phenotypes using secondary analysis of publicly available GWAS cohorts is a cost-effective and efficient way to gain insights into biological pathways underlying sleep regulation. This knowledge is necessary for development of novel diagnostics and therapeutics for sleep disorders and for understanding causal relationships between sleep and associated chronic diseases to enable effective interventions for these conditions.

Public Health Relevance

Sleep is an essential component of daily life, but little is known about its regulation at the molecular level. Furthermore, disruptions in sleep amount, quality or timing contribute to many common diseases, such as heart disease, diabetes, obesity and mood disorders. We will use a powerful human genetics approach on publicly collected genetic and sleep data to find genes that contribute to differences in sleep characteristics among individuals. This will help to identify pathways important in sleep regulation that should inform basic knowledge and lead to better prevention, diagnosis and therapies for sleep-related disorders and chronic diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL121728-01A1
Application #
8758062
Study Section
Special Emphasis Panel (ZRG1-PSE-Q (56))
Program Officer
Laposky, Aaron D
Project Start
2014-08-01
Project End
2016-04-30
Budget Start
2014-08-01
Budget End
2015-04-30
Support Year
1
Fiscal Year
2014
Total Cost
$130,500
Indirect Cost
$55,500
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Lane, Jacqueline M; Liang, Jingjing; Vlasac, Irma et al. (2017) Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits. Nat Genet 49:274-281
Cade, Brian E; Gottlieb, Daniel J; Lauderdale, Diane S et al. (2016) Common variants in DRD2 are associated with sleep duration: the CARe consortium. Hum Mol Genet 25:167-79
Chang, Anne-Marie; Bjonnes, Andrew C; Aeschbach, Daniel et al. (2016) Circadian gene variants influence sleep and the sleep electroencephalogram in humans. Chronobiol Int 33:561-73
Lane, Jacqueline M; Chang, Anne-Marie; Bjonnes, Andrew C et al. (2016) Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology. Diabetes 65:1741-51
Eichler, Florian S; Li, Jiankang; Guo, Yiran et al. (2016) CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids. Brain 139:1666-72
Lane, Jacqueline M; Vlasac, Irma; Anderson, Simon G et al. (2016) Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank. Nat Commun 7:10889
Tare, Archana; Lane, Jacqueline M; Cade, Brian E et al. (2014) Sleep duration does not mediate or modify association of common genetic variants with type 2 diabetes. Diabetologia 57:339-46