DNA METHYLATION OF CIRCADIAN GENES AND MARKERS OF CARDIOMETABOLIC RISK IN FEMALE HOSPITAL WORKERS: AN EXPLORATORY STUDY
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Authors
Ahmadi, Salman
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Type
thesis
Language
eng
Keyword
DNA methylation , circadian genes , cardiometabolic risk , cardiovascular disease , night shift work
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Abstract
Objectives: To investigate if DNA methylation of circadian genes, a potential causal mechanism in the pathway linking night shift work and cardiovascular disease (CVD), is differentially associated with markers of cardiometabolic risk and temporal changes in markers of cardiometabolic risk by shift work status among female hospital personnel. Methods: A cross-sectional study was conducted from 2019-2020 at Kingston Health Sciences Centre (KHSC) in Kingston, ON, Canada. Participants were 74 female hospital personnel (38 day workers, 36 night shift workers) who participated in a previous cross-sectional study conducted from 2011-2014 (N = 330) at KHSC. Participants completed a questionnaire to provide data on sociodemographic, lifestyle, and health characteristics, as well as lifetime occupational history to assess current and past day and night shift work. DNA methylation levels of circadian genes (1150 cytosine-guanine (CpG) sites across 22 circadian genes) were measured in newly collected fasting blood samples (2019-2020) using the Illumina Infinium MethylationEPIC BeadChip microarray, while markers of cardiometabolic risk were measured in both newly collected samples and samples collected during the previous study (2011-2014). Multiple linear and quantile regression modeling was conducted to investigate associations between methylation levels at individual CpG sites (β-values) and markers of cardiometabolic risk and changes in markers of cardiometabolic risk over a 5-9 year time period, while considering effect modification by shift work status. The false discovery rate was applied to account for multiple comparisons (q ≤ 0.20). Results: Two CpG sites [cg06758649 (CRY1) and cg06899802 (CSNK1A1)] were differentially associated with waist circumference and body mass index by shift work status, eight CpG sites [cg26103512 (CSNK1D), cg03941313 (CSNK1E), cg18217763 (CSNK1E), cg16682686 (DEC1), cg12061096 (RORA), cg10133825 (RORA), cg19652148 (RORA), and cg22904654 (RORA)] were differentially associated with low-density lipoprotein (LDL) cholesterol concentration by shift work status, and one CpG site [cg20791744 (NR1D2)] was differentially associated with the change in diastolic blood pressure between 2011-2014 and 2019-2020 by shift work status. Conclusion: Our findings suggest that day and night shift workers experience different associations between DNA methylation of circadian genes and markers of cardiometabolic risk which may contribute to the increased risk of CVD observed among night shift workers.
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ProQuest PhD and Master's Theses International Dissemination Agreement
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Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.