Gene‒environment interaction effect of hypothalamic‒pituitary‒adrenal axis gene polymorphisms and job stress on the risk of sleep disturbances

Min Zhao; Yuxi Wang; Yidan Zeng; Huimin Huang; Tong Xu; Baoying Liu; Chuancheng Wu; Xiufeng Luo; Yu Jiang

doi:10.7717/peerj.17119

Gene‒environment interaction effect of hypothalamic‒pituitary‒adrenal axis gene polymorphisms and job stress on the risk of sleep disturbances

PeerJ. 2024 Mar 20:12:e17119. doi: 10.7717/peerj.17119. eCollection 2024.

Authors

Min Zhao^#¹, Yuxi Wang^#¹, Yidan Zeng¹, Huimin Huang¹, Tong Xu², Baoying Liu¹, Chuancheng Wu¹, Xiufeng Luo³, Yu Jiang¹

Affiliations

¹ Department of Public Health, Fujian Medical University, Fuzhou, China.
² Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
³ Fuzhou Municipal Center for Disease Control and Prevention, Fuzhou, China.

^# Contributed equally.

Abstract

Background: Studies have shown that chronic exposure to job stress may increase the risk of sleep disturbances and that hypothalamic‒pituitary‒adrenal (HPA) axis gene polymorphisms may play an important role in the psychopathologic mechanisms of sleep disturbances. However, the interactions among job stress, gene polymorphisms and sleep disturbances have not been examined from the perspective of the HPA axis. This study aimed to know whether job stress is a risk factor for sleep disturbances and to further explore the effect of the HPA axis gene × job stress interaction on sleep disturbances among railway workers.

Methods: In this cross-sectional study, 671 participants (363 males and 308 females) from the China Railway Fuzhou Branch were included. Sleep disturbances were evaluated with the Pittsburgh Sleep Quality Index (PSQI), and job stress was measured with the Effort-Reward Imbalance scale (ERI). Generalized multivariate dimensionality reduction (GMDR) models were used to assess gene‒environment interactions.

Results: We found a significant positive correlation between job stress and sleep disturbances (P < 0.01). The FKBP5 rs1360780-T and rs4713916-A alleles and the CRHR1 rs110402-G allele were associated with increased sleep disturbance risk, with adjusted ORs (95% CIs) of 1.75 [1.38-2.22], 1.68 [1.30-2.18] and 1.43 [1.09-1.87], respectively. However, the FKBP5 rs9470080-T allele was a protective factor against sleep disturbances, with an OR (95% CI) of 0.65 [0.51-0.83]. GMDR analysis indicated that under job stress, individuals with the FKBP5 rs1368780-CT, rs4713916-GG, and rs9470080-CT genotypes and the CRHR1 rs110402-AA genotype had the greatest risk of sleep disturbances.

Conclusions: Individuals carrying risk alleles who experience job stress may be at increased risk of sleep disturbances. These findings may provide new insights into stress-related sleep disturbances in occupational populations.

Keywords: Gene‒environment interaction; HPA axis; Job stress; Rail workers; Sleep disturbance.

MeSH terms

Cross-Sectional Studies
Female
Gene-Environment Interaction*
Humans
Hypothalamo-Hypophyseal System
Male
Occupational Stress* / epidemiology
Pituitary-Adrenal System
Polymorphism, Genetic / genetics
Sleep / genetics

Grants and funding

This study was supported by the Fujian Medical University’s Research Foundation for Talented Scholars (grant number XRCZX2018011) and the Fuzhou Science and Technology Project (grant number 2022-S-033). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.