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.

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.

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.

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. Competing Interest Statement The authors have declared no competing interest. Funding Statement Data collection in FinnTwin12 has been supported by the National Institute on Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to Richard J. Rose, and AA015416 to Danielle Dick and Jessica Salvatore) and the Academy of Finland (grants 100499, 205585, 118555, 141054, 264146, 308248, 312073, 336823, and 352792 to Jaakko Kaprio). Jaakko Kaprio acknowledges support by the Academy of Finland (grants 265240, 263278). S.K. was in part funded by the Funded by the European Union (ERC-2022-CoG-BrainScape-101086188). Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency (ERCEA). Neither the European Union nor the granting authority can be held responsible for them. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committee of the Department of Public Health of the University of Helsinki (Helsinki, Finland) and the Institutional Review Board of Indiana University (Bloomington, Indiana, USA) approved the FinnTwin12 study protocol from the start of the cohort. The ethical approval of the ethics committee of the Helsinki University Central Hospital District (HUS) is the most recent and covers the most recent data collection (early midlife) (HUS/2226/2021, dated September 22, 2021). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data availability statement The FinnTwin12 data are not publicly available due to the restrictions of informed consent. However, the FinnTwin12 data are available through the Institute for Molecular Medicine Finland (FIMM) Data Access Committee (DAC) (fimm-dac{at}helsinki.fi) for authorized researchers who have IRB/ethics approval and an institutionally approved study plan. To ensure the protection of privacy and compliance with national data protection legislation, a data use/transfer agreement is needed, the content and specific clauses of which will depend on the nature of the requested data. Requests will be addressed in a reasonable time frame (generally two to three weeks), and the primary mode of data access is by either personal visit or remote access to a secure server. Codes for major analyses are available at https://github.com/doge73/viewfactor_dep).