Interactions of the CSF3R polymorphism and early stress on future orientation: evidence for the differential model of stress-related growth

• Main Authors: Yiqun Gan (Author), Lizhong Wang (Author), Yidi Chen (Author), Lei Zheng (Author), Xiaoli Wu (Author), Gang Chen (Author), Yueqin Hu (Author)
• Format: Book
• Published: Cambridge University Press, 2024-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1017/S2045796024000581; 2045-7960; 2045-7979
• Keywords: CSF3R; future orientation; gene × environment interaction; genome-wide interaction studies; threshold model of stress-related growth; Neurosciences. Biological psychiatry. Neuropsychiatry; RC321-571; Public aspects of medicine; RA1-1270
• Source: Epidemiology and Psychiatric Sciences, Vol 33 (2024)

Abstract Aims This study aims to explore the concept of future orientation, which encompasses individuals' thoughts about the future, goal-setting, planning, response to challenges and behavioural adjustments in evolving situations. Often viewed as a psychological resource, future orientation is believed to be developed from psychological resilience. The study investigates the curvilinear relationship between childhood maltreatment and future orientation while examining the moderating effects of genotype. Methods A total of 14,675 Chinese adults self-reported their experiences of childhood maltreatment and their future orientation. The influence of genetic polymorphism was evaluated through genome-wide interaction studies (GWIS; genome-wide association study [GWAS] using gene × environment interaction) and a candidate genes approach. Results Both GWAS and candidate genes analyses consistently indicated that rs4498771 and its linked single-nucleotide polymorphisms, located in the intergenic area surrounding CSF3R, significantly interacted with early trauma to influence future orientation. Nonlinear regression analyses identified a quadratic or cubic association between future orientation and childhood maltreatment across some genotypes. Specifically, as levels of childhood maltreatment increased, future orientation declined for all genotypes. However, upon reaching a certain threshold, future orientation exhibited a rebound in individuals with specific genotypes. Conclusions The findings suggest that individuals with certain genotypes exhibit greater resilience to childhood maltreatment. Based on these results, we propose a new threshold model of stress-related growth.