Moderating effects of PER3 gene DNA methylation on the association of sleep quality with mental health in Chinese young adults

Background: Poor sleepers have a higher prevalence of mental health problems, and vice versa. However, the mechanisms underlying this association remain unknown. We aimed to examine the bidirectional association between sleep quality and mental health, and further explore the moderating effects of PER3 gene DNA methylation on the association.

Methods: This prospective longitudinal study was conducted from April 2019 to May 2021, integrated questionnaire and blood sample data from 2 universities in Anhui and Jiangxi Provinces. The current study recruited 1179 young adults at baseline and conducted the follow-up survey among 1135 half a year later. The sleep quality and depressive symptoms, anxiety symptoms, and stress symptoms were assessed using a questionnaire at baseline and follow-up. Blood samples were collected at baseline, and MethyTarget™ was used to detect the PER3 gene DNA methylation level. A cross-lag model was used to examine the bidirectional association between sleep quality and mental health. The PROCESS plug-in of SPSS software was used to analyse the moderating effects of PER3 gene DNA methylation.

Results: Cross-lagged analyses suggested a significant bidirectional relationship between poor sleep quality and depressive symptoms, anxiety symptoms, and stress symptoms. Sleep quality at baseline was a significant predictor of depressive symptoms (β = 0.344, P < 0.001), anxiety symptoms (β = 0.348, P < 0.001), and stress symptoms (β = 0.324, P < 0.001) half a year later. Depressive symptoms (β = 0.049, P < 0.001), anxiety symptoms (β = 0.055, P < 0.001), and stress symptoms (β = 0.063, P < 0.001) at baseline were also significant predictors of poor sleep quality half a year later. Furthermore, PER3 gene DNA methylation has negative moderating effects between sleep quality at baseline and depressive symptoms (β = -11.706, P = 0.012), anxiety symptoms (β = -10.289, P = 0.019), and stress symptoms (β = -10.799, P = 0.024) half a year later and a sex difference. Among boys, PER3 gene DNA methylation has positive moderating effects between anxiety symptoms at baseline and sleep quality (β = 3.337, P = 0.018) half a year later. However, there was no association between mental health at baseline and sleep quality half a year later among girls.

Conclusion: Bidirectional relationships were identified between sleep quality and mental health among Chinese young adults during the study period. DNA methylation evidence supports a negative moderating effect of PER3 gene DNA methylation on the relationship between sleep quality at baseline and mental health half a year later and had sex differences. Among boys, PER3 gene DNA methylation had positive moderating effects between anxiety symptoms at baseline and sleep quality half a year later. These findings point to the importance of circadian clock gene DNA methylation in the relationship between sleep quality and mental health.