Gene-environment interplay in the relationship between the visibility of the environment and self-reported depression in early midlife: a Finnish twin cohort study.

Background: Depression is a major public health concern with a complex etiology, which may also be influenced by the living environment. The first-person visibility represents the most direct way of influence from the physical environment. Objectives: We aim to investigate the effect of the visibility of the environment at the residence on self-reported depression among early midlife adults, as well as underlying gene-environment interplay. Methods: The study used 1867 participants who completed the early midlife follow-u p (mean age: 37.2 years) of the FinnTwin12 cohort. The visibility of the environment at the residence was segmented into three visibility factors: sky, tree, and building. Linear regression was fitted between visibility factors and self-reported depression. Molecular methods using polygenetic risk score and twin design (univariate modeling and bivariate moderation modeling) were applied to explore the gene-environment correlation and interaction. Findings: In males, a higher proportion of building visibility factor was associated with more depression (beta: 0.20, 95% CI: 0.03, 0.36). Univariate twin models estimated that additive genetic factors accounted for 46%, 29%, and 49% of the variance in sky, tree, and building visibility factors, respectively. Bivariate moderation analyses revealed strong gene-environment interactions between all three visibility factors and self-reported depression in females, while in males, interaction was observed by the building visibility factor. Conclusion: Urban design should consider building density and other related characteristics to promote mental well-being. The complex gene-environment interplay informs the need for tailored interventions that account for genetic susceptibility and processes by which persons select their inhabitats.