The past decades, studies indicated that night shift work is associated with adverse health effects, however, molecular mechanisms underlying these effects are poorly understood. A few previous studies have hypothesized a role for DNA-methylation (DNAm) in this relationship. We performed a cross-sectional epigenome-wide association study, to investigate if night shift work is associated with genome-wide DNAm changes and DNAm-based biological age acceleration, based on previously developed so-called 'epigenetic clocks.' Short term (2-6 years) and intermediate term (10-16 years) night shift workers, along with age and sex matched dayworkers (non-shift workers) were selected from the Lifelines Cohort Study. For genome-wide methylation analysis the Infinium Methylation EPIC array (Ilumina) was used. Linear regression analyses were used to detect differences in methylation at individual CpG-sites associated with night shift work. Pathway analysis was performed based on KEGG pathways and predictions of age acceleration in night shift workers were performed based on four previously developed epigenetic age calculators. Only in women, differences in methylation at individual CpG-sites were observed between night shift workers and non-shift workers. Most of these differentially methylated positions (DMPs) were observed in intermediate term night shift workers. Pathway analysis shows involvement of pathways related to circadian rhythm and cellular senescence. Increased age acceleration was observed only in short-term night shift workers (men and women). This might be indicative of adaptation to night shift work or a so-called healthy worker effect. In conclusion, these results show that DNA methylation changes are associated with night shift work, specifically in women.
Keywords: DNA-methylation; Night shift work; circadian rhythm; epigenetic clock.