TY - JOUR
T1 - Differential DNA methylation in recovery from shift work disorder
AU - Lahtinen, Alexandra
AU - Häkkinen, Antti
AU - Puttonen, Sampsa
AU - Vanttola, Päivi
AU - Viitasalo, Katriina
AU - Porkka-Heiskanen, Tarja
AU - Härmä, Mikko
AU - Paunio, Tiina
N1 - Funding Information:
We are grateful to Auli Toivola for conducting molecular experiments. The authors wish to acknowledge the CSC—IT Center for Science, Finland, for computational resources, and Viljo Soo at the core facility of the Institute of Genomics, University of Tartu, for running the methylation experiments. This work was supported by grants from the Academy of Finland (Grant No. 290039), EVO (TYH2016242), Päivikki and Sakari Sohlberg Foundation, and Finnish Work Environment Fund (111102). A.H. is funded by Academy of Finland grant no. 322927. M.H. and S.P. are funded by NordForsk grant no. 74809. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-021-82627-0
DO - 10.1038/s41598-021-82627-0
M3 - Article
C2 - 33536559
AN - SCOPUS:85100400992
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 2895
ER -