DNA methylation pathway associated with insufficient sleep

Show simple item record

dc.contributor Helsingin yliopisto, Lääketieteellinen tiedekunta fi
dc.contributor University of Helsinki, Faculty of Medicine en
dc.contributor Helsingfors universitet, Medicinska fakulteten sv
dc.contributor.author Lahtinen, Alexandra
dc.date.issued 2018
dc.identifier.uri URN:NBN:fi:hulib-201811153537
dc.identifier.uri http://hdl.handle.net/10138/278381
dc.description.abstract 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. en
dc.language.iso eng
dc.publisher Helsingin yliopisto fi
dc.publisher University of Helsinki en
dc.publisher Helsingfors universitet sv
dc.subject insufficient sleep
dc.subject DNA methylation
dc.subject shift work disorder
dc.subject pathway analysis
dc.subject epigenome-wide association study
dc.title DNA methylation pathway associated with insufficient sleep en
dc.type.ontasot pro gradu -tutkielmat fi
dc.type.ontasot master's thesis en
dc.type.ontasot pro gradu-avhandlingar sv
dct.identifier.urn URN:NBN:fi:hulib-201811153537

Files in this item

Files Size Format View
Lahtinen_Alexandra_pro_gradu_2018.pdf 1.797Mb application/pdf View/Open

This item appears in the following Collection(s)

Show simple item record