Distinct biological signature and modifiable risk factors underlie the comorbidity between major depressive disorder...

Area of Science:

• Genetics
• Psychiatry
• Cardiology

Background:

• Major depressive disorder (MDD) and cardiovascular disease (CVD) frequently co-occur, increasing patient morbidity and mortality.
• Understanding the shared biological underpinnings is crucial for developing effective prevention and treatment strategies.

Purpose of the Study:

• To investigate the shared genetic liability between MDD and atherosclerotic CVD.
• To identify biological mechanisms and modifiable risk factors contributing to MDD-CVD comorbidity.

Main Methods:

• Multivariate genome-wide association analysis (mGWAS) was employed to analyze shared genetic risk between MDD and atherosclerotic CVD.
• Tissue and brain cell-type enrichment analyses were performed to pinpoint specific biological pathways.

Main Results:

• Seven genetic loci were identified, highlighting shared genetic risk factors between MDD and atherosclerotic CVD.
• Genetic liability for MDD showed causal effects on CVD risk, partly mediated by inflammatory, metabolic, and psychosocial factors.
• Distinct tissue and brain cell-type enrichments suggested the thalamus's involvement, pointing towards an immunometabolic subtype of MDD.

Conclusions:

• Shared genetic factors contribute significantly to the comorbidity of MDD and CVD.
• MDD confers a causal risk for CVD, influenced by metabolic and lifestyle factors.
• Identifying an immunometabolic subtype of MDD offers potential targets for CVD prevention in affected individuals.