Exploration of genome-wide DNA methylation profiles in night shift workers

ABSTRACT

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:

• Night shift work
• DNA-methylation
• epigenetic clock
• circadian rhythm

Acknowledgments

The authors wish to acknowledge the services of the Lifelines Cohort study, the contributing research centers delivering data to Lifelines, and all the study participants.

Author contributions

P.W., M.D. and L.K. designed the study. M.D. and L.K. developed the shift work questionnaire. C.O. assisted in sample handling and preparation. P.W. performed all data analyses. P.W., M.D. and L.K. wrote the article. All authors revised the article and approved the final version.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Protection of research participants

Approval of the Lifelines Cohort study was obtained from the Medical Ethics Committee of the University Medical Center Groningen, The Netherlands. Informed consent was obtained from all participants.

Data availability

Data used in this study were obtained from or collected by the Lifelines Cohort Study. Data is available upon request according to their permissions for use. Please see www.lifelines.nl/researcher.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15592294.2022.2152637.

Additional information

Funding

This study was funded by the Dutch Ministry of Social Affairs and Employment [KV11.16], the Ministry of Health, Welfare and Sport & The National Institute for Public Health of the Netherlands [S/010003], and through Bioclock, a project within the NWA-ORC programme of the Dutch Research Council [project number 1292.19.077]. The funding bodies had no role in the study design, the collection, analysis, and interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication. The Lifelines initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG), Groningen University, and the provinces in the north of the Netherlands (Drenthe, Friesland, Groningen);Ministerie van Sociale Zaken en Werkgelegenheid;Rijksinstituut voor Volksgezondheid en Milieu;nederlandse organisatie voor wetenschappelijk onderzoek;