Nature geneticsAug 26, 2026

Shared genetic influences between major depression and related physical illnesses

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 28, 2026

Abstract

Three disease clusters accounted for 47% of the genetic risk for major depressive disorder (MDD).

The gastrointestinal disease cluster had the strongest association with MDD (β=0.63, P=3.04×10^-30).
Independent genetic loci were identified that are associated with the shared genetic risk between each disease cluster and MDD.
Different pleiotropic components were revealed among the disease clusters in relation to MDD.
Unique biological pathways, drug groups, cell types, and genes were found to be associated with each disease-MDD cluster.
Genetic connections suggest that the gut-brain axis may play a significant role in the comorbidity of physical diseases in MDD.

Simplified

Major depressive disorder (MDD) is characterized by substantial comorbidity with medical conditions. To achieve better outcomes for patients with MDD, an improved understanding of the mechanisms underlying pervasive comorbidities is required. Here, to this end, we mapped patterns of pleiotropy by defining four clusters of physical diseases (cardiovascular, metabolic, gastrointestinal and immune) and analyzed their genetic relationships with MDD using genomic structural equation modeling. Three disease clusters exhibited independent associations with MDD and accounted for 47% of MDD h²_SNP, with the gastrointestinal disease cluster having the strongest association (β = 0.63, s.e. = 0.05, P = 3.04 × 10^-30). In addition, we identified independent loci associated with the shared genetic liability between each disease cluster and MDD, revealing different pleiotropic components. Characterization of these loci revealed previously unidentified associations with MDD and physical disease traits, along with unique biological pathways, drug groups, cell types and genes associated with each disease-MDD cluster. Our findings reveal genetic connections implicating the gut-brain axis as a key mechanism underlying the comorbidity of physical diseases in MDD. This work advances our understanding of MDD by highlighting unique and shared genetic components across different disease systems.

Full Text

Full text is available at the source.

View Full Text ↗

Featured in

Gut-Brain AxisIssue #52

Probiotics cut a key Alzheimer's protein in older adults with early memory problems

↗

Shared genetic influences between major depression and related physical illnesses

Abstract

Full Text

Featured in

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the gut-brain axis brief