Genetic studies of accelerometer-based sleep measures in 85,670 individuals yield new insights into human sleep behaviour
Jones SE., Hees VTV., Mazzotti DR., Marques-Vidal P., Sabia S., der Spek AV., Dashti HS., Engmann J., Kocevska D., Tyrrell J., Beaumont RN., Hillsdon M., Ruth KS., Tuke MA., Yaghootkar H., Sharp S., Jie Y., Harrison JW., Freathy RM., Murray A., Luik AI., Amin N., Lane JM., Saxena R., Rutter MK., Tiemeier H., Kutalik Z., Kumari M., Frayling TM., Weedon MN., Gehrman P., Wood AR.
<jats:title>ABSTRACT</jats:title><jats:p>Sleep is an essential human function but its regulation is poorly understood. Identifying genetic variants associated with quality, quantity and timing of sleep will provide biological insights into the regulation of sleep and potential links with disease. Using accelerometer data from 85,670 individuals in the UK Biobank, we performed a genome-wide association study of 8 accelerometer-derived sleep traits, 5 of which are not accessible through self-report alone. We identified 47 genetic associations across the sleep traits (<jats:italic>P</jats:italic><5×10<jats:sup>-8</jats:sup>) and replicated our findings in 5,819 individuals from 3 independent studies. These included 26 novel associations for sleep quality and 10 for nocturnal sleep duration. The majority of newly identified variants were associated with a single sleep trait, except for variants previously associated with restless legs syndrome that were associated with multiple sleep traits. Of the new associated and replicated sleep duration loci, we were able to fine-map a missense variant (p.Tyr727Cys) in <jats:italic>PDE11A</jats:italic>, a dual-specificity 3’,5’-cyclic nucleotide phosphodiesterase expressed in the hippocampus, as the likely causal variant. As a group, sleep quality loci were enriched for serotonin processing genes and all sleep traits were enriched for cerebellar-expressed genes. These findings provide new biological insights into sleep characteristics.</jats:p>