BACKGROUND Shift work has been associated with increased risk of age-related morbidity and mortality. Biological age, estimated using DNA methylation (DNAm), may quantify the biological consequences of shift work on the risk of age-related disease. We examined whether prior employment in shift-working occupations was associated with epigenetic age acceleration. METHODS In a sample of non-Hispanic White women aged 35-74 (n = 2574), we measured DNAm using the Illumina Infinium Human450 BeadChip and calculated DNAm age using three established epigenetic clocks. Age-acceleration metrics were derived by regressing DNAm age on chronological age and predicting the residuals. Using linear regression, we estimated associations between shift work history and age acceleration. We also conducted an epigenome-wide association study using robust linear-regression models corrected with false discovery rate (FDR) q-values. RESULTS Approximately 7% of women reported any shift work. Higher age acceleration was observed for a 1-year increase in overall [β = 0.11, 95% confidence interval (CI): 0.02-0.21] and night-specific shift work (β = 0.12, 95% CI: 0.03-0.21). The association was strongest for ≥10 years of night shift work (β = 3.16, 95% CI: 1.17-5.15). From the epigenome-wide association study, years of overall and night shift work were associated with DNAm at 66 and 85 CpG sites (FDR < 0.05), respectively. Years of night shift work was associated with lower methylation of a CpG in the gene body of ZFHX3 (cg04994202, q = 0.04), a gene related to circadian rhythm. CONCLUSIONS Shift work was associated with differential CpG site methylation and with differential DNAm patterns, measured by epigenetic age acceleration, consistent with long-term negative health effects.

中文翻译：

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轮班工作，DNA甲基化和表观遗传年龄。

背景技术轮班工作与与年龄有关的发病率和死亡率的风险增加有关。使用DNA甲基化（DNAm）估算的生物年龄可以量化轮班工作对与年龄有关的疾病的风险的生物学后果。我们检查了轮班工作之前的工作是否与表观遗传的年龄加速有关。方法在样本中，年龄在35-74岁的非西班牙裔白人女性（n = 2574）中，我们使用Illumina Infinium Human450 BeadChip测量DNAm，并使用三个已建立的表观遗传时钟来计算DNAm年龄。年龄加速指标是通过按时间顺序对DNAm年龄进行回归并预测残差来得出的。使用线性回归，我们估计了轮班工作历史和年龄加速之间的关联。我们还使用错误发现率（FDR）q值校正的鲁棒线性回归模型进行了表观基因组范围的关联研究。结果约有7％的女性报告有任何轮班工作。总体上，[1 = 0.11，95％置信区间（CI）：0.02-0.21]和夜间特定的轮班工作（β= 0.12，95％CI：0.03-0.21）的增加1年观察到更高的年龄加速。在≥10年的夜班工作中，这种关联最强（β= 3.16，95％CI：1.17-5.15）。从表观基因组范围的关联性研究来看，多年的整体工作和夜班工作分别与66和85个CpG位点的DNAm相关（FDR <0.05）。多年的夜班工作与ZFHX3（cg04994202，q = 0.04）的基因体中CpG的甲基化程度较低有关，ZFHX3是与昼夜节律有关的基因。