DNA methylation pathway associated with insufficient sleep

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http://urn.fi/URN:NBN:fi:hulib-201811153537
Titel: DNA methylation pathway associated with insufficient sleep
Författare: Lahtinen, Alexandra
Medarbetare: Helsingin yliopisto, Lääketieteellinen tiedekunta
University of Helsinki, Faculty of Medicine
Helsingfors universitet, Medicinska fakulteten
Utgivare: Helsingin yliopisto
Datum: 2018
Språk: eng
Permanenta länken (URI): http://urn.fi/URN:NBN:fi:hulib-201811153537
http://hdl.handle.net/10138/278381
Nivå: pro gradu-avhandlingar
Abstrakt: The need to sleep is physiologically regulated and lack of sleep results in impaired daily performance and feeling of tiredness. If sleep disturbance persists for a long time, the risk of many somatic and mental disorders increases. The study of the key molecular processes triggered by insufficient sleep could foster the assessment and enhance the methods of prevention and cure of these long-term health risks. Both insufficient and mistimed sleep have been shown to strongly affect cell transcriptome in animal models and in the studies of selected human cohorts. However, our understanding of the epigenetic modifications, particularly DNA methylation, triggered by the sleep loss remains limited. Here, we performed an epigenome-wide association study in the whole blood samples of men from the general population reporting lack of sleep and of men diagnosed with a shift work disorder. We combined the results from the two independent samples and identified a set of differentially methylated positions (DMPs) common for both cohorts. We further analyzed this set of DMPs by various computational tools, in order to explore altered biological pathways in individuals suffering from lack of sleep. As a result, we discovered a neurological pathway enriched for genes with DMPs, suggesting that curtailed sleep may result in the changes in processes related to synaptic plasticity. We also observed the loss of methylation in the majority of DMPs, in agreement with an earlier observation on the night shift workers. In order to investigate the effect of DNA methylation on gene expression, we performed correlational analyses of M values of the DMPs and the levels of corresponding gene expression. Since methylation levels might fluctuate according to the time of the blood sampling, we also studied the correlation of the DMPs with the time of the sampling. The analysis of genomic locations of the DMPs revealed enrichment of genomic loci involved in syndromes with symptoms of disturbances in visual processing and regulation of circadian rhythm. Our findings suggest that there is a distinctive pattern of genes showing diversity of epigenetic modifications in relation to insufficient sleep in men. The molecular mechanisms behind the observed associations require further investigation, both in general population based samples comprising both genders or occupational cohorts, and in experimental data.
Subject: insufficient sleep
DNA methylation
shift work disorder
pathway analysis
epigenome-wide association study


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