Investigating shared genetic architecture between major depressive disorder and central obesity
Authors' conclusion
Our findings establish pleiotropy between MDD and WHR, implicating dysregulated immunometabolic pathways as shared mechanisms. Prioritized drug targets represent translatable opportunities for comorbidity management.
Study context
- Population
- Large-scale genome-wide association study summary statistics for major depressive disorder (MDD) and waist-hip ratio (WHR)
- Outcome
- Shared genetic architecture between MDD and WHR
Methodological detailsgenome-wide association study summary statistics, cross-trait genetic correlation, pleiotropic variant discovery, drug target prioritization
- Genome-wide association study summary statistics
- Cross-trait genetic correlation
- Pleiotropic variant discovery
- Drug target prioritization
Main finding
As reported in the abstract
Genetic correlation between MDD and WHR (rg), p = 4.18 × 10-5
0.11
Pleiotropic loci identified by cross-trait analysis, incl. a novel variant (rs2855812, intronic to MICB)
26
Pleiotropic loci confirmed by colocalization
6
Forward MR: MDD associated with increased WHR (β), 95% CI: 0.014-0.143; p = 0.017
0.079
Further findings
- Drug prioritization identified agents able to be repurposed targeting MICB, PSORS1C1 and C6orf15
- Enrichment analyses highlighted immune pathways
Original publication
Investigating shared genetic architecture between major depressive disorder and central obesity. Obesity (Silver Spring). Published 27 July 2025. doi:10.
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