Shared genetic loci between depression and cardiometabolic traits

Area of Science:

• Genetics
• Psychiatry
• Cardiology

Background:

• Epidemiological and clinical studies link depression with cardiovascular disease (CVD) risk factors, noting poorer outcomes in CVD patients with depression.
• The genetic underpinnings of the relationship between depression and cardiovascular phenotypes remain largely unknown.

Purpose of the Study:

• To investigate genome-wide and individual locus overlap between depression, coronary artery disease (CAD), and cardiovascular risk factors.
• To identify shared genetic variants and loci influencing these complex traits.

Main Methods:

• Utilized bivariate causal mixture model (MiXeR) for genome-wide polygenic overlap quantification.
• Employed conditional/conjunctional false discovery rate (pleioFDR) to identify shared genetic loci.
• Analyzed genome-wide association study (GWAS) summary statistics for depression, CAD, and nine cardiovascular risk factors.
• Performed functional annotation of genetic loci using FUnctional Mapping and Annotation (FUMA).

Main Results:

• Significant polygenic overlap was observed between depression and body-mass index (9.5K shared variants), and between systolic blood pressure and depression (2K shared variants).
• Identified 79 unique loci associated with depression and either CAD or cardiovascular risk factors using conjFDR.
• Found six genomic loci jointly associated with depression and CAD, alongside numerous loci linked to blood pressure, lipids, type 2 diabetes, and c-reactive protein.
• Loci associated with increased depression risk also showed increased risk for CAD, higher total cholesterol, LDL, and c-reactive protein levels.

Conclusions:

• Demonstrated substantial polygenic overlap between depression, coronary artery disease, and several cardiovascular risk factors.
• Suggested shared molecular mechanisms, including alpha-linolenic acid metabolism for type 2 diabetes, underlying the depression-CVD association.
• Highlighted potential genetic links contributing to the increased cardiovascular disease risk observed in individuals with depression.