Decoding Gene–Environment Interaction in Psychiatric Disorders: From Cross-Disorder Genetic Architecture to Precision Psychiatry

Psychiatric disorders are highly heritable yet profoundly shaped by environmental exposures, with increasing evidence suggesting that shared genetic architectures underlie multiple diagnostic categories. Large-scale genome-wide association studies (GWAS), biobank resources, and advances in statistical genetics have revealed extensive pleiotropy and genetic correlations across disorders such as schizophrenia, bipolar disorder, major depressive disorder, substance use disorders, and suicidality. Meanwhile, environmental risk factors—including early-life adversity, substance exposure, stress, and social determinants—modulate genetic susceptibility through complex gene–environment (G×E) interactions. Recent developments in multi-ancestry genomics, polygenic risk modeling, multi-omics integration, and longitudinal cohort designs now provide unprecedented opportunities to dissect how genetic liability and environmental contexts jointly shape psychiatric phenotypes, disease trajectories, and treatment response.The goal of this Research Topic is to advance our understanding of how gene–environment interplay contributes to the aetiology, heterogeneity, and clinical outcomes of psychiatric disorders across diagnostic boundaries. Despite substantial progress in identifying genetic risk loci, translating these findings into mechanistic insight and clinical utility remains challenging, particularly when environmental modulation is overlooked. This topic aims to integrate recent advances in cross-disorder GWAS, polygenic risk scores, longitudinal modelling, and multi-omics approaches to illuminate dynamic G×E mechanisms. Special emphasis will be placed on transdiagnostic frameworks, multi-ancestry analyses to reduce health disparities, and approaches that link genetic liability to intermediate phenotypes such as cognition, brain imaging, behaviour, and stress reactivity. Ultimately, this Research Topic seeks to bridge genetic discovery with precision psychiatry by identifying biologically informed risk stratification strategies and modifiable environmental targets for prevention and intervention.This Research Topic welcomes original research, systematic reviews, meta-analyses, and methodological papers addressing gene–environment interactions and cross-disorder genetic mechanisms in psychiatric disorders.• Cross-phenotype and transdiagnostic genetic architecture of psychiatric disorders• Gene–environment interaction and correlation studies using population cohorts or biobanks• Polygenic risk scores combined with environmental, clinical, or behavioural data• Multi-omics integration (e.g., epigenomics, transcriptomics, proteomics) in psychiatric genetics• Causal inference approaches linking environmental exposures, genetic liability, and psychiatric outcomes• Translational implications for risk prediction, prevention, and personalized treatment Topic editors: Qiang WANG, Hongsheng Gui, Justin Tubbs, Yamin Zhang Source: https://www.frontiersin.org/research-topics/77064/decoding-gene-environment-interaction-in-psychiatric-disorders-from-cross-disorder-genetic-architecture-to-precision-psychiatry