Systematic evaluation of the environmental effect on depressive symptoms in late adolescence and early adulthood: exposome-wide association study and twin modeling

The exposome represents the totality of environmental effects, but systematic evaluation between it and depressive symptoms is scant. We sought to comprehensively identify the association of the exposome with depressive symptoms in late adolescence and early adulthood and determine genetic and environmental covariances between them. Based on the population-based FinnTwin12 cohort (3025 participants in young adulthood and 4127 at age 17), the exposome-wide association study (ExWAS) design was used to identify significant exposures from 12 domains. Bivariate Cholesky twin models were fitted to an exposome score and depressive symptoms. In ExWASes, 29 and 46 exposures were significantly associated with depressive symptoms in young adulthood and at age 17, respectively, and family-related exposures were the most influential. Twin models indicated considerable genetic and environmental covariances between the exposome score and depressive symptoms. The findings underscore the systematic approach of the exposome and the consideration of relevant genetic effects. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was partly funded by the European Union Horizon 2020 research and innovation program under grant agreement No 874724 (Equal-Life). Equal-Life is part of the European Human Exposome Network. Data collection in FinnTwin12 has been supported by the National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to Richard J. Rose) and the Academy of Finland (grants 100499, 205585, 118555, 141054, 264146, 308248, 312073, 336823, and 1352792 to Jaakko Kaprio). Jaakko Kaprio acknowledges support by the Academy of Finland (grants 265240, 263278). ### 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), the ethics committee of the Helsinki University Central Hospital District (Helsinki, Finland), and the Institutional Review Board of Indiana University (Bloomington, Indiana, USA) gave ethical approval for this work. 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 The FinnTwin12 data is not publicly available due to the restrictions of informed consent. However, the FinnTwin12 data is available through the Institute for Molecular Medicine Finland (FIMM) Data Access Committee (DAC) (fimm-dac@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.