Influence of harm-avoidance traits on anxiety: coping style as a mediator and CK1 gene polymorphism as a moderator

Objective The mechanisms linking personality and anxiety remain incompletely understood. Thus, it is necessary to investigate the potential psychological and biological mechanisms. The present study examined the mediation effect of coping styles and moderation effect of the casein kinase 1 epsilon (CSNK1E; traditionally abbreviated CK1) gene polymorphism in this relationship. Methods The CK1 gene rs135745C/G polymorphism was genotyped in 556 healthy Chinese adults, and the personality traits, anxiety levels, and coping styles were assessed using the Tridimensional Personality Questionnaire, State-Trait Anxiety Inventory, and Simplified Coping Style Questionnaire, respectively. Results State and trait anxiety were positively related to the harm avoidance (HA) trait (both p < 0.01). Positive coping mediated the association between HA and its four subscales and both state and trait anxiety (all p < 0.01), and passive coping mediated the association between HA1, HA2, and HA4 and both state and trait anxiety (all p < 0.01). The rs135745 polymorphism moderated the association of HA with state ( p = 0.008) and trait anxiety ( p = 0.001). Simple slope analyses showed that the direction of the HA–anxiety association differed between genotype groups: it was negative in the small CC subgroup (n=8) (state: β = -1.3788, p = 0.0485; trait: β = -1.7363, p = 0.0105) and positive in G allele carriers (state: β = 0.4751, p < 0.001; trait: β = 0.5186, p < 0.001). Conclusions The present study demonstrates that Coping styles play a mediating role between HA and both state and trait anxiety in healthy Chinese adults, and provides preliminary evidence that the CK1 gene polymorphism may moderate this pathway, suggesting a potential gene–behavior interaction in the development of anxiety; the CC-specific pattern requires validation in larger cohorts.