Summary: Study sheds light on DNA methylation related to sleep deprivation in those with shift-work disorder.
Source: University of Helsinki
Long-term sleep deprivation is detrimental to health, increasing the risk of psychiatric and somatic disorders, such as depression and cardiovascular diseases. And yet, little is known about the molecular biological mechanisms set in motion by sleep deprivation which underlie related adverse health effects.
In a recently published study, the University of Helsinki, the Finnish Institute for Health and Welfare, the Finnish Institute of Occupational Health and the Finnair airline investigated dynamic changes to DNA methylation in shift workers. DNA methylation denotes epigenetic regulation that modifies gene function and regulates gene activity without changing the sequence of bases in the DNA.
Short-term genetic changes caused by DNA methylation are not well known. While methylation is connected with our surroundings, more research is needed on how the environment affects epigenetic regulation and gene function.
The recently published study provides researchers with new information on both DNA methylation and the biological processes that have an impact on a sleep disorder related to shift work (shift work disorder, or SWD).
The study was published in the esteemed Scientific Reports publication series.
Changes to DNA methylation can mediate infections caused by sleep deprivation
A total of 32 shift workers participated in the study, of whom 21 suffered from shift work disorder and 11 were in the control group. Dynamic changes to DNA methylation were investigated through a genome-wide analysis during work and after a holiday period.
Changes to DNA methylation which affected gene function were identified in study subjects suffering from a sleep disorder caused by shift work. The findings demonstrated that rest and recovery during holiday periods also resulted in the restoration of DNA methylation in cases where changes had been observed during the work period.
The study proved the dynamic nature of DNA methylation, which was particularly emphasised in the activity of NMDA glutamate receptors. The strongest evidence was gained from the GRIN2C receptor: the methylation level of a specific CpG base pair in the regulatory region was lower during the work period in subjects suffering from shift work disorder. However, this change was reversed after the holiday period.
“Based on the results, we can deduce that changes to the DNA methylation of white blood cells are associated with shift work disorder. These changes, such as low methylation levels observed during the work period, are probably linked to sleep deprivation and related inflammatory consequences which DNA changes may mediate,” says doctoral student Alexandra Lahtinen, MSc, from the University of Helsinki.
“Sufficient rest and recovery are important for everyone, but especially important for people with a background of long-term sleep deprivation due to, for example, living habits or irregular working conditions. Having said that, it’s positive that the subjects recovered from at least some of the changes related to shift work disorder observed in the study,” says Professor Tiina Paunio from the University of Helsinki and the Finnish Institute for Health and Welfare, who was the principal investigator of the study.
About this sleep and genetics research news
Source: University of Helsinki Contact: Tiina Paunio – University of Helsinki Image: The image is in the public domain
Differential DNA methylation in recovery from shift work disorder
The human DNA methylome is responsive to our environment, but its dynamics remain underexplored.
We investigated the temporal changes to DNA methylation (DNAme) in relation to recovery from a shift work disorder (SWD) by performing a paired epigenome-wide analysis in an occupational cohort of 32 shift workers (25 men, age = 43.8 ± 8.8 years, 21 SWD cases). We found that the effect of vacation on DNAme was more prominent in the SWD-group as compared to controls, with respect to the amount of significantly differentially methylated positions (DMPs; Punadj < 0.05) 6.5 vs 3.7%, respectively.
The vast majority (78%) of these DMPs were hypomethylated in SWD but not in controls (27%) during the work period. The Gene Ontology Cellular component “NMDA glutamate receptor” (PFDR < 0.05) was identified in a pathway analysis of the top 30 genes in SWD. In-depth pathway analyses revealed that the Reactome pathway “CREB phosphorylation through the activation of CaMKII” might underlie the recovery. Furthermore, three DMPs from this pathway, corresponding to GRIN2C, CREB1, and CAMK2B, correlated with the degree of recovery (Punadj < 0.05).
Our findings provide evidence for the dynamic nature of DNAme in relation to the recovery process from a circadian disorder, with biological relevance of the emerging pathways.