Research Questions:
1) Unique genetic markers of depression-anxiety comorbidity vs. single disorders?
2) The interaction of environmental stressors (trauma, urban pollution) with genetic risks?
3) Biomarkers (brain/blood) to predict comorbidity progression?
4) Tailored treatments of comorbidity?
Objectives:
1) Genetic Architecture: Perform GWAS on 20K comorbidity cases vs. 100K controls (UK Biobank) to identify novel loci; Build comorbidity-specific polygenic scores (PGS).
2) Gene-Environment Interplay: Quantify interactions between trauma/pollution and genetic risks .
3) Mechanistic Pathways: Test if amygdala reactivity (fMRI) or blood biomarkers (cortisol) mediate genetic risk.
4) Clinical Translation: Develop ML risk models (PGS + environment) and compare SSRI response by genotype.
Scientific Rationale:
Depression and anxiety co-occur in 50-60% of patients, worsening outcomes. Twin studies suggest shared genetics, but comorbidity-specific mechanisms remain unknown. UK Biobank’s multimodal data (genomics, brain imaging, health records) uniquely enables:
Decoding genetic-environmental synergies driving comorbidity;
Identifying early biomarkers for prevention;
Personalizing treatments (e.g., avoiding ineffective SSRIs).
This project transforms comorbidity from a descriptive label to a biologically defined subtype, advancing precision psychiatry.