Center for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
Sleep. 2022 Oct 10;45(10). doi: 10.1093/sleep/zsac180.
Sleep occurs universally and is a biological necessity for human functioning. The consequences of diminished sleep quality impact physical and physiological systems such as neurological, cardiovascular, and metabolic processes. In fact, people impacted by common complex diseases experience a wide range of sleep disturbances. It is challenging to uncover the underlying molecular mechanisms responsible for decreased sleep quality in many disease systems owing to the lack of suitable sleep biomarkers. However, the discovery of a genetic component to sleep patterns has opened a new opportunity to examine and understand the involvement of sleep in many disease states. It is now possible to use major genomic resources and technologies to uncover genetic contributions to many common diseases. Large scale prospective studies such as the genome wide association studies (GWAS) have successfully revealed many robust genetic signals associated with sleep-related traits. With the discovery of these genetic variants, a major objective of the community has been to investigate whether sleep-related traits are associated with disease pathogenesis and other health complications. Mendelian Randomization (MR) represents an analytical method that leverages genetic loci as proxy indicators to establish causal effect between sleep traits and disease outcomes. Given such variants are randomly inherited at birth, confounding bias is eliminated with MR analysis, thus demonstrating evidence of causal relationships that can be used for drug development and to prioritize clinical trials. In this review, we outline the results of MR analyses performed to date on sleep traits in relation to a multitude of common complex diseases.
睡眠普遍存在，是人类机能的生物学必需。睡眠质量下降的后果会影响神经系统、心血管和代谢等生理系统。事实上，患有常见复杂疾病的人会经历各种睡眠障碍。由于缺乏合适的睡眠生物标志物，许多疾病系统中导致睡眠质量下降的潜在分子机制难以被揭示。然而，睡眠模式的遗传成分的发现为研究和理解睡眠在许多疾病状态中的作用开辟了新的机会。现在，利用主要的基因组资源和技术，可以发现许多常见疾病的遗传贡献。全基因组关联研究（GWAS）等大型前瞻性研究已经成功揭示了许多与睡眠相关特征相关的稳健遗传信号。随着这些遗传变异的发现，研究人员的一个主要目标是调查睡眠相关特征是否与疾病发病机制和其他健康并发症有关。孟德尔随机化（MR）是一种分析方法，它利用遗传位点作为代理指标来建立睡眠特征与疾病结果之间的因果关系。鉴于这些变异是在出生时随机遗传的，因此 MR 分析消除了混杂偏差，从而证明了可以用于药物开发和优先进行临床试验的因果关系证据。在这篇综述中，我们概述了迄今为止针对与多种常见复杂疾病相关的睡眠特征进行的 MR 分析的结果。
