Why sleep?

In the course of their life, the average person sleeps for more than 25 years. Along with its conservation across species, this suggests that sleep is likely to play a vitally important role in normal functioning. Great advances have been made in understanding the circadian and homeostatic factors that regulate sleep, but there is still much that is unknown about its putative functions. Although it is known to be involved with a broad range of processes (including memory consolidation, neuroprotective actions, hormonal function, and interactions with the cardiovascular and immune systems), ‘sleep’ is really an umbrella term for a heterogeneous set of interacting processes that need to be better characterized and understood.

Individual differences in sleep

People vary considerably in their typical quality and quantity of sleep. On one level, brain activity as measured by the electroencephalogram (EEG) is a heritable “fingerprint”, aspects of which correlate with a range of clinical, demographic and cognitive variables. On another level, individuals suffering from disorders of sleep (including sleep apnea, insomnia, hypersomnia and narcolepsy) can exhibit markedly aberrant sleep patterns. The precise genetic basis for most of this clinically meaningful variability is largely unknown, however.

Sleep and health

Individual differences in sleep (especially lack of sleep) have been associated with a host of chronic medical conditions including obesity, diabetes, hypertension, heart disease and – ultimately – with shortened life expectancy. For some disorders (e.g. major depressive disorder and bipolar disorder) sleep problems are core clinical features. However, the direction of these associations is typically unclear. Do sleep problems lead to disease, or disease to abnormal sleep? Or does a third factor – such as shared genetic basis – give rise both to the sleep and health phenotypes? Delineating these causal networks will be important because they can provide a basis for identifying targets for intervention and patient stratification.

Program in Sleep and Neuropsychiatric Genetics

We are initiating a Program in Sleep and Neuropsychiatric Genetics to tackle some of the questions raised above. Specifically, we will embark on pursuing three broad goals:

To Characterize Normal and Abnormal Variation in Sleep
  • Data generation: compilation of genetically-informative datasets
  • In silico phenotyping: characterizing sleep EEG in large samples
  • Building a pipeline: develop and deploy analysis tools for large sleep datasets
To Determine the Genetic Basis of Variation in Sleep
  • Phenotype-to-genotype: initiating discovery genetics projects for sleep phenotypes
  • Genotype-to-phenotype: screening disease-associatied genes for mediating sleep phenotypes
  • Computational/statistical methods development: using genetics to unpack heterogeneity
To Elucidate the Genetic and Environmental Causal Networks that Relate Sleep and Complex Disorders
  • Novel sleep epidemiology: mining big data for correlates of sleep phenotypes
  • Pleiotropic genes: searching for shared genetic basis between sleep and disease phenotypes
  • Causal modeling: untangling cause from effect and confounder
Core Members

To complement the focus on brain activity during sleep in relation to psychiatric disease, we also aim to work synergistically with parallel efforts within BWH focused on different aspects of sleep and physical health. Reflecting this, key members and their research interests are listed below:

  • Dr Shaun Purcell: neuropsychiatric genetics and computational/statistical method development, including sleep EEG
  • Dr Susan Redline: genetic epidemiology of sleep disorders and links to physical health
  • Dr Richa Saxena: genetics, sleep, circadian rhythms and cardiovascular disease
  • Dr Brian Cade: bioinformatics, statistical genetics and sleep/circadian
Affiliations and Partnerships

As a cross-disciplinary initiative, the Program spans the Departments of Psychiatry and Medicine, and is part of the Division for Sleep and Circadian Disorders. We aim to complement existing strong programs including the Programs in Sleep and Cardiovascular Medicine and Sleep Medicine Epidemiology, and the broader Division of Sleep Medicine, in order integrate a focus on neuropsychiatric outcomes, such that the resulting collaborative research will address more holistically the function of sleep in health and disease.

We will also have a close partnership with the Center for Analysis for Complex Sleep Signals, in which methodological expertise in signal processing and modeling can be brought together with expertise in statistical genetics and epidemiology.