This K23 award will allow Dr. Watson to become an investigator proficient in genetic epidemiology and the design and conduct of interdisciplinary research on gene-environment interactions in sleep medicine. The training and research activities will focus on complex environmental and genetic influences on habitual sleep duration and the impact of sleep restriction on appetite-regulating hormones and insulin resistance. This application proposes an intensive, 5-year program of mentored research and formal training activities to enhance Dr. Watson's skills and experience in: 1) genetic epidemiology including twin research methods, 2) sleep deprivation research, and 3) training in the analysis of the frequently sampled intravenous glucose tolerance test and the physiology of appetite regulating hormones. The research component of this career development award targets habitual sleep restriction and its metabolic ramifications. Obesity and insulin resistance, characteristics of the metabolic syndrome, appear to be associated with habitual sleep curtailment, but the physiologic mechanisms and genetic factors underlying the link are unclear. Using the population based University of Washington Twin Registry, the Specific Aims are to: 1) identify the genetic and environmental influences on habitual sleep duration, and 2) examine the relationship between sleep restriction and appetite-regulating hormones, abdomnial adioposity, insulin sensitivity, lipid levels, blood pressure, and quantitative 11 (i-hydroxysteroid dehydrogenase-1 gene expression in sleep restricted individuals.
Specific Aim 1 will be addressed with a classical twin study and Specific Aim 2 will use a co-twin control design. This project will establish a pathway for Dr. Watson's future investigations and hopefully benefit clinicians and researchers seeking to understand the untoward consequences of sleep restriction. The University of Washington is an exceptional environment for Dr. Watson to gain the skills needed to achieve his goals. The training component uses academic resources including the School of Public Health and Community Medicine's Institute for Public Health Genetics, the NIH-funded General Clinical Research Center, the NIDDK-funded Diabetes and Endocrinology Research Center and Molecular Genetics Core Laboratory, and the Division of Metabolism, Endocrinology, and Nutrition. Dr. Watson's sponsors, mentors, and consultants are all highly regarded and respected scientists.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-R (O1))
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Lewin, Daniel S
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University of Washington
Schools of Medicine
United States
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Watson, N F; Buchwald, D; Delrow, J J et al. (2017) Transcriptional Signatures of Sleep Duration Discordance in Monozygotic Twins. Sleep 40:
Watson, Nathaniel F; Horn, Erin; Duncan, Glen E et al. (2016) Sleep Duration and Area-Level Deprivation in Twins. Sleep 39:67-77
Wrede, Joanna E; Mengel-From, Jonas; Buchwald, Dedra et al. (2015) Mitochondrial DNA Copy Number in Sleep Duration Discordant Monozygotic Twins. Sleep 38:1655-8
Barclay, Nicola L; Watson, Nathaniel F; Buchwald, Dedra et al. (2014) Moderation of genetic and environmental influences on diurnal preference by age in adult twins. Chronobiol Int 31:222-31
Watson, Nathaniel F; Harden, Kathryn Paige; Buchwald, Dedra et al. (2014) Sleep duration and depressive symptoms: a gene-environment interaction. Sleep 37:351-8
Watson, Nathaniel F; Buchwald, Dedra; Harden, Kathryn Paige (2013) A twin study of genetic influences on diurnal preference and risk for alcohol use outcomes. J Clin Sleep Med 9:1333-9
Watson, Nathaniel F; Harden, Kathryn Paige; Buchwald, Dedra et al. (2012) Sleep duration and body mass index in twins: a gene-environment interaction. Sleep 35:597-603
Watson, Nathaniel F; Ton, Thanh G N; Koepsell, Thomas D et al. (2012) Birth order and narcolepsy risk among genetically susceptible individuals: a population-based case-control study. Sleep Med 13:310-3
Viola-Saltzman, Mari; Watson, Nathaniel F (2012) Traumatic brain injury and sleep disorders. Neurol Clin 30:1299-312
Watson, Nathaniel F (2011) Searching for the missing heritability. Sleep 34:1453-4

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