Summary: Researchers have identified genetic links between a range of health conditions and sleep disturbances.
Source: Mass General.
Researchers from the United States and the United Kingdom have, for the first time, mapped genetic links connecting sleep disturbances—such as insomnia and excessive daytime sleepiness—with multiple medical conditions, including obesity, restless legs syndrome and schizophrenia.
The study was led by Jacqueline Lane, PhD, a postdoctoral fellow at Massachusetts General Hospital (MGH), with joint senior authors Richa Saxena, PhD, assistant professor of Anesthesia at MGH and Harvard Medical School, and Martin K. Rutter, MD, FRCP, senior lecturer in Cardiometabolic Medicine at The University of Manchester. The team published their findings in Nature Genetics.
The researchers analyzed data from more than 112,000 participants in the UK Biobank. Each participant reported their typical sleep duration, symptoms of insomnia, and levels of daytime sleepiness, and contributed genetic data. The study also incorporated clinical and physical measurements such as body mass index and waist circumference, along with medical history information.
Using genome-wide association analyses, the team identified genomic regions associated with self-reported sleep traits. For insomnia symptoms, the strongest association was found near a gene previously linked to restless legs syndrome, a neurological condition that causes an irresistible urge to move the legs—often worse at night. Other loci showed sex-specific effects, appearing significant either in women or in men.
Distinct genetic links also emerged between longer sleep duration and increased schizophrenia risk, and between higher levels of daytime sleepiness and measures of adiposity such as BMI and waist circumference. The results further suggest shared underlying biology between insomnia and major depression, as well as between insomnia and abnormal glucose metabolism.
These discoveries represent a significant advance in sleep biology and in understanding how genetic variation contributes to health risks associated with sleep disturbance. The research was funded by the U.S. National Institutes of Health and The University of Manchester’s Research Innovation Fund.
Sleep disturbances and the conditions they intersect with carry substantial public health impact. For example, roughly one in four British adults are classified as obese, and the National Health Service treats about 280,000 people with schizophrenia at any given time; individuals diagnosed with schizophrenia face elevated risks of suicide within years of diagnosis. By clarifying molecular links between sleep traits and these disorders, the current study provides new avenues for research into prevention, diagnosis and treatment.
Lead and senior investigators emphasized the translational potential of these findings. Dr. Rutter noted that identifying molecular connections is an important step toward understanding the biological basis of these conditions. Dr. Lane highlighted the value of the UK Biobank as a resource for large-scale investigations into health and genetics. Dr. Saxena pointed out the current clinical limitations—most sleep-targeted treatments are symptomatic, primarily sedatives—and expressed hope that these genetic insights could inspire new, more targeted interventions for sleep-related disorders and their comorbidities. The authors stress that follow-up studies are needed to validate mechanisms and explore therapeutic targets.
Funding: Supported by the National Institutes of Health and the University of Manchester Research Innovation Fund.
Source: Terri Ogan – Mass General
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Original Research: “Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits” by Jacqueline M. Lane et al.; published online December 19, 2016. DOI: 10.1038/ng.3749
Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits
Chronic sleep disturbances are associated with cardiometabolic disease, psychiatric disorders and increased mortality, affecting an estimated 25–30% of adults worldwide. Although environmental factors significantly influence self-reported sleep duration and disruption, these traits are heritable. Identifying the genetic contributors can improve understanding of sleep biology, reveal mechanisms linking sleep to disease, and guide the development of new therapies.
This study reports single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in 112,586 UK Biobank participants. The investigators discovered loci associated with insomnia symptoms near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males; a locus associated with excessive daytime sleepiness near AR–OPHN1; and composite sleep-trait associations near PATJ (INADL) and HCRTR2. The team also replicated a previously reported locus for sleep duration at PAX8.
Genetic correlation analyses revealed a positive correlation between longer sleep duration and schizophrenia risk (rg = 0.29, P = 1.90 × 10−13), and between greater excessive daytime sleepiness and adiposity measures (BMI: rg = 0.20, P = 3.12 × 10−9; waist circumference: rg = 0.20, P = 2.12 × 10−7). These results highlight shared genetics linking sleep traits with neuropsychiatric and metabolic conditions.
This study leverages large-scale genetic and phenotypic data to clarify the molecular architecture of sleep disturbance traits and their overlap with important health conditions. Further research is needed to translate these genetic findings into clinical interventions and to explore biological mechanisms in diverse populations.