PER1-related inflammatory signaling links night shift exposure to lower lung function in coal miners

Cumulative night-shift exposure may disrupt circadian homeostasis and adversely relate to respiratory health. In a cross-sectional analysis of 9,464 coal miners, we found that greater cumulative night-shift exposure was associated with lower lung function after accounting for cumulative respirable dust exposure. Mendelian randomization analyses supported a potential causal link between shift work and reduced lung function and further indicated that genetically predicted lower lung function was associated with higher chronic obstructive pulmonary disease (COPD) risk. In a coal miner subgroup, lower PER1 expression partly accounted for the associations of cumulative night-shift exposure with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Public transcriptomic and single-cell analyses showed lower PER1 expression in COPD and lung cancer-related datasets and suggested links to NF-κB-related inflammatory signaling. These findings suggest that PER1 -related inflammatory signaling may represent a candidate molecular link between occupational circadian disruption and respiratory health impairment.