Investigating the Biology of Depression and Coronary Artery Disease using Genetics, Genomics, and Electronic Health Record Data

Abstract

Coronary artery disease (CAD) and depression are highly prevalent and frequently comorbid. Approximately 40% of adults who are initially diagnosed with either CAD or depression will also develop the other condition. Moreover, a diagnosis of Major Depressive Disorder (MDD) is associated with increased 18-month cardiac mortality and CAD-MDD comorbidity reduces lifespan by 15-20 years. However, despite the commonness and high mortality rate of CAD-depression comorbidity, the relationship between CAD and depression remains poorly understood. Using several genetics and genomic approaches such as transcriptome wide association scan (TWAS), longitudinal modelling, genome-wide association scan (GWAS), polygenic scores, and pathway enrichment we show that depression and CAD become comorbid though inflammatory mechanisms. Using these approaches our work confirms the role of inflammatory pathways and immune markers, particularly WBC count in mediating the (m)dCAD comorbidity. Our work highlights the importance of integrating mental health care with cardiovascular disease care and motivates future work.