[DSRP Evidence](https://dsrpevidence.org/)

# Dissecting pleiotropy between major depressive disorder and physical disease comorbidities

Woodward et al., 2026, Nature Genetics — Genetics

Patterns: [Distinctions](https://dsrpevidence.org/pattern/distinctions), [Systems](https://dsrpevidence.org/pattern/systems), [Relationships](https://dsrpevidence.org/pattern/relationships)

## In short

The whole genetic architecture of a disorder is decomposed into distinct disease-cluster categories, and the shared genetic liability between those categories and the disorder constitutes a causal, mechanistic relationship rather than mere co-occurrence.

## What they found (results)

Genomic structural equation modeling identified four physical-disease clusters (cardiovascular, metabolic, gastrointestinal, immune), three of which independently associate with major depressive disorder and jointly explain 47% of its SNP-heritability, with the gastrointestinal cluster showing the strongest genetic correlation, implicating a gut-brain axis mechanism.

These researchers were not testing DSRP. The finding is theirs; the correspondence to DSRP is drawn by this site.

[Source](https://doi.org/10.1038/s41588-026-02735-3)