Genes associated with depression and coronary artery disease are enriched for inflammation and cardiomyopathy-associated pathways

Background Depression and Coronary Artery Disease (CAD) are highly comorbid conditions. Approximately 40% of individuals who have one diagnosis will also develop the other within their lifetime. Prior research indicates that polygenic risk for depression increases the odds of developing CAD even in the absence of clinical depression. However, the specific genes and pathways involved in comorbid depression-CAD remain unknown. Results We identified genes that are significantly associated with both depression and CAD, and are enriched for pathways involved in inflammation and for previous association with cardiomyopathy. We observed increased rate of prevalent, but not incident, cardiomyopathy cases in individuals with comorbid depression-CAD compared to those with CAD alone in three electronic large health record (EHR) datasets. Conclusions The results of our study implicate genetically regulated inflammatory mechanisms in depression-CAD. Our results also raise the hypothesis that depression-associated CAD may be enriched for cardiomyopathy. Clinical Perspective What’s New? Gene associations shared between depression and CAD are enriched for prior association with cardiomyopathy phenotypes. Cardiomyopathy is significantly more prevalent in individuals with comorbid depression-CAD than in CAD or depression alone. What are the Clinical Implications? Our work suggests that individuals with comorbid depression-CAD may benefit from screening for cardiomyopathy.