Genetics of Complex Traits, College of Medicine and Health, University of Exeter, Exeter, EX2 5DW, UK.
Netherlands eScience Center, Amsterdam, 1098 XG, The Netherlands.
Nat Commun. 2019 Apr 5;10(1):1585. doi: 10.1038/s41467-019-09576-1.
Sleep is an essential human function but its regulation is poorly understood. Using accelerometer data from 85,670 UK Biobank participants, we perform a genome-wide association study of 8 derived sleep traits representing sleep quality, quantity and timing, and validate our findings in 5,819 individuals. We identify 47 genetic associations at P < 5 × 10, of which 20 reach a stricter threshold of P < 8 × 10. These include 26 novel associations with measures of sleep quality and 10 with nocturnal sleep duration. The majority of identified variants associate with a single sleep trait, except for variants previously associated with restless legs syndrome. For sleep duration we identify a missense variant (p.Tyr727Cys) in PDE11A as the likely causal variant. As a group, sleep quality loci are enriched for serotonin processing genes. Although accelerometer-derived measures of sleep are imperfect and may be affected by restless legs syndrome, these findings provide new biological insights into sleep compared to previous efforts based on self-report sleep measures.
睡眠是人类的基本功能之一,但它的调节机制仍未被充分理解。我们使用来自 85670 名英国生物银行参与者的加速计数据,对 8 种衍生的睡眠特征进行了全基因组关联研究,这些特征代表了睡眠质量、数量和时间,并在 5819 个人中验证了我们的发现。我们在 P<5×10 处鉴定出 47 个遗传关联,其中 20 个达到更严格的 P<8×10 的阈值。这些关联包括 26 个与睡眠质量测量相关的新关联和 10 个与夜间睡眠时间相关的关联。除了先前与不安腿综合征相关的变异外,大多数已识别的变异与单一睡眠特征相关。对于睡眠时间,我们在 PDE11A 中鉴定出一个错义变异(p.Tyr727Cys),它可能是因果变异。作为一个整体,睡眠质量位点富集了 5-羟色胺处理基因。尽管基于加速计的睡眠测量并不完美,并且可能受到不安腿综合征的影响,但与之前基于自我报告睡眠测量的研究相比,这些发现为睡眠提供了新的生物学见解。