Division of Neuroscience & Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, UK(2).
Division of Nursing, Midwifery & Social Work, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, UK.
Mech Ageing Dev. 2020 Jun;188:111253. doi: 10.1016/j.mad.2020.111253. Epub 2020 May 1.
Human chronotype, the temporal pattern of daily behaviors, is influenced by postnatal seasonal programming and ageing. The aim of this study was to investigate genetic variants that are associated with season of birth programming and longitudinal chronotype change. Longitudinal sleep timing and genotype data from 1449 participants were collected for up to 27 years. Gene-environment interaction analysis was performed for 445 candidate single nucleotide polymorphisms that have previously been associated with chronotype. Associations were tested using linear mixed model. We identified 67 suggestively significant genomic loci that have genotype-ageing interaction and 25 genomic loci that may have genotype-season of birth interaction in determining chronotype. We attempted to replicate the results using longitudinal data of the UK Biobank from approximately 30,000 participants. Biological functions of these genes suggest that epigenetic regulation of gene expression and neural development may have roles in these processes. The strongest associated gene for sleep trajectories was ALKBH5, which has functions of DNA repair and epigenetic regulation. A potential candidate gene for postnatal seasonal programming was SIRT1, which has previously been implicated in postnatal programming, ageing and longevity. Genetic diversity may explain the heterogeneity in ageing-related change of sleep timing and postnatal environmental programming of later-life chronotype.
人类的生物钟，即日常行为的时间模式，受到产后季节编程和衰老的影响。本研究旨在探讨与出生季节编程和纵向生物钟变化相关的遗传变异。从 1449 名参与者中收集了长达 27 年的纵向睡眠时间和基因型数据。对先前与生物钟相关的 445 个候选单核苷酸多态性进行了基因-环境相互作用分析。使用线性混合模型进行关联测试。我们确定了 67 个具有基因型-年龄相互作用的提示性显著基因组位点和 25 个可能具有基因型-出生季节相互作用的基因组位点，以确定生物钟。我们尝试使用来自大约 30000 名参与者的英国生物库的纵向数据来复制这些结果。这些基因的生物学功能表明，基因表达和神经发育的表观遗传调控可能在这些过程中起作用。与睡眠轨迹最相关的基因是 ALKBH5，它具有 DNA 修复和表观遗传调控的功能。SIRT1 可能是产后季节编程的潜在候选基因，它以前曾被牵涉到产后编程、衰老和长寿中。遗传多样性可能解释了与衰老相关的睡眠时间变化和晚年生活生物钟的产后环境编程的异质性。
