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Night shift work has been linked to increased risk of cardiovascular disease (CVD); however, the underlying mechanisms remain unclear. A compelling yet understudied mechanism involves differential DNA methylation of circadian genes. To investigate the relevance of this mechanism, we conducted an exploratory cross-sectional study of 74 female hospital personnel (38 day workers, 36 night shift workers). Sociodemographic, lifestyle, and health characteristics as well as shift work status and history were determined through self-report. Fasting blood samples were collected to measure markers of cardiometabolic risk and DNA was extracted to measure DNA methylation of 1150 cytosine-guanine (CpG) sites across 22 circadian genes. Associations between methylation levels at individual CpG sites (β-values) and markers of cardiometabolic risk were analyzed while considering effect modification by shift work status. The false discovery rate was applied to account for multiple comparisons ( q  ≤ 0.20). Two CpG sites [cg06758649 ( CRY1 ) and cg06899802 ( CSNK1A1 )] were differentially associated with waist circumference and body mass index by shift work status, and eight CpG sites [cg26103512 ( CSNK1D ), cg03941313 ( CSNK1E ), cg18217763 ( CSNK1E ), cg16682686 ( DEC1 ), cg12061096 ( RORA ), cg10133825 ( RORA ), cg19652148 ( RORA ), and cg22904654 ( RORA )] were differentially associated with LDL cholesterol concentration by shift work status (all  q  ≤ 0.20). Our findings suggest that the relationship between DNA methylation of circadian genes and cardiometabolic risk differs by day and night shift worker status, which may contribute to mechanisms of increased risk of CVD observed among night shift workers.

DNA methylation of circadian genes and markers of cardiometabolic risk in female hospital workers: An exploratory study