Bidirectional genetic associations between chronotype and shift work: A Mendelian randomization study

Shift work, particularly night shifts, disrupts circadian rhythms and contributes to various adverse health outcomes. However, the degree of individual adaptability varies considerably, suggesting complex interactions between genetic factors, such as chronotype, and shift work exposure. To explore these interactions, we conducted a bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data from European populations. We examined causal associations between chronotype and shift work patterns (limited, intermittent, regular). A significant inverse causal effect was identified for intermittent shift work influencing morning chronotype (IVW: β =-0.0032, SE = 0.0013, p = 0.0114; weighted median: β = -0.0041, SE = 0.0018, p = 0.0213). This suggests that intermittent shift work may impact circadian preferences genetically linked to chronotype. Conversely, genetic predisposition toward morningness exhibited a notable but statistically non-significant inverse relationship with regular shift work. Our findings highlight that shift work and chronotype interact bidirectionally, potentially via circadian disruption and melatonin dysregulation. These insights could inform targeted health protection strategies for shift workers. Further studies should confirm these genetic interactions across diverse populations and clarify the underlying chronobiological mechanisms to enhance occupational health policies.