Genes associated with depression and coronary artery disease are enriched for cardiomyopathy and inflammatory phenotypes

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. Despite the high prevalence of the comorbidity, the specific genes and pathways remain unknown. Here, by mapping known variants to genes, we identified genes, followed by pathways, that are associated with both depression and CAD. Next, we investigated the phenotypic consequences of the shared pathways in an electronic health record (EHR)-based setting. We identified 185 genes that were significantly associated with both depression and CAD and were enriched for inflammatory and cardiomyopathy phenotypes. We observed an increased rate of prevalent cardiomyopathy cases in individuals with comorbid depression–CAD compared with those with CAD alone in three large EHR datasets. 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.