Shared Genetic Factors Between Stress-related Disorders and Cardiovascular Disease

Area of Science:

• Genetics
• Cardiovascular Medicine
• Psychiatry

Background:

• Comorbidity between stress-related disorders (SRDs) and cardiovascular disease (CVD) is clinically significant.
• Understanding shared genetic factors is crucial for integrated prevention and treatment strategies.
• Current evidence on the genetic basis of SRD-CVD comorbidity is limited.

Purpose of the Study:

• To investigate shared genetic liability between SRDs and six CVD subtypes.
• To identify pleiotropic loci, genes, and biological pathways contributing to SRD-CVD comorbidity.
• To explore the genetic overlap using large-scale population data and genetic association studies.

Main Methods:

• Integration of Swedish national registers (n=4,123,631) and UK Biobank (n=502,291) data.
• Genome-wide association study (GWAS) summary statistics and polygenic risk score (PRS) analyses.
• Familial coaggregation, genetic correlation, Mendelian randomization (MR), and cross-trait analyses were performed.

Main Results:

• Familial coaggregation supported shared genetic influences, with associations weakening among less related relatives.
• SRD polygenic risk scores predicted increased CVD risk (ORs=1.05-1.09), and positive genetic correlations (rg=0.09-0.35) were observed for all SRD-CVD pairs.
• Seventeen pleiotropic loci and 16 prioritized genes were identified, enriched in hemostasis, coagulation, circulatory development, and telomere maintenance pathways.

Conclusions:

• Shared genetic liability, driven by pleiotropic loci, contributes to the comorbidity of SRDs and CVD.
• Findings support a genetic comorbidity framework for SRDs and CVD.
• Identified candidate genes and pathways provide targets for future experimental research and therapeutic development.