Biological and clinical insights from genetics of insomnia symptoms.
Lane JM., Jones SE., Dashti HS., Wood AR., Aragam KG., van Hees VT., Strand LB., Winsvold BS., Wang H., Bowden J., Song Y., Patel K., Anderson SG., Beaumont RN., Bechtold DA., Cade BE., Haas M., Kathiresan S., Little MA., Luik AI., Loudon AS., Purcell S., Richmond RC., Scheer FAJL., Schormair B., Tyrrell J., Winkelman JW., Winkelmann J., HUNT All In Sleep None., Hveem K., Zhao C., Nielsen JB., Willer CJ., Redline S., Spiegelhalder K., Kyle SD., Ray DW., Zwart J-A., Brumpton B., Frayling TM., Lawlor DA., Rutter MK., Weedon MN., Saxena R.
Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly understood. Here we identified 57 loci for self-reported insomnia symptoms in the UK Biobank (n = 453,379) and confirmed their effects on self-reported insomnia symptoms in the HUNT Study (n = 14,923 cases and 47,610 controls), physician-diagnosed insomnia in the Partners Biobank (n = 2,217 cases and 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n = 83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis and of genes expressed in multiple brain regions, skeletal muscle, and adrenal glands. Evidence of shared genetic factors was found between frequent insomnia symptoms and restless legs syndrome, aging, and cardiometabolic, behavioral, psychiatric, and reproductive traits. Evidence was found for a possible causal link between insomnia symptoms and coronary artery disease, depressive symptoms, and subjective well-being.