Decoding depression by exploring the exposome-genome edge amidst COVID-19 lockdown

Abstract

Risk of depression increased in the general population after the COVID-19 pandemic outbreak. By examining the interplay between genetics and individual environmental exposures during the COVID-19 lockdown, we have been able to gain an insight as to why some individuals are more vulnerable to depression, while others are more resilient. This study, conducted on a Spanish cohort of 9218 individuals (COVICAT), includes a comprehensive non-genetic risk analysis, the exposome, complemented by a genomics analysis in a subset of 2442 participants. Depression levels were evaluated using the Hospital Anxiety and Depression Scale. Together with Polygenic Risk Scores (PRS), we introduced a novel score; Poly-Environmental Risk Scores (PERS) for non-genetic risks to estimate the effect of each cumulative score and gene-environment interaction. We found significant positive associations for PERSSoc (Social and Household), PERSLife (Lifestyle and Behaviour), and PERSEnv (Wider Environment and Health) scores across all levels of depression severity, and for PRSB (Broad depression) only for moderate depression (OR 1.2, 95% CI 1.03-1.40). On average OR increased 1.2-fold for PERSEnv and 1.6-fold for PERLife and PERSoc from mild to severe depression level. The complete adjusted model explained 16.9% of the variance. We further observed an interaction between PERSEnv and PRSB showing a potential mitigating effect. In summary, stressors within the social and behavioral domains emerged as the primary drivers of depression risk in this population, unveiling a mitigating interaction effect that should be interpreted with caution.

This study was conducted in the framework of the support “Incentius a l’Avaluació de Centres CERCA (in_CERCA)”, according to the resolution on 20th Dec 2019 from the president of the Executive Board of the AGAUR. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. This study makes use of data generated by the GCAT-Genomes for Life. Cohort study of the Genomes of Catalonia Germans Trias i Pujol Research Institute (IGTP). IGTP is part of the CERCA Program/Generalitat de Catalunya. GCAT is supported by Acción de Dinamización del ISCIII-MINECO and the Ministry of Health of the Generalitat of Catalunya (ADE 10/00026); the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2021 SGR 01537 (SGR-GRIMtra)). A full list of the investigators who contributed to the generation of the GCAT data is available from www.genomesforlife.com.