This study investigated the phenome-wide consequences of a genetic liability to MDD and loneliness in BioVU, which is a deeply phenotyped large-scale EHR collection with linked genotype data. We discovered strong associations between polygenic scores for MDD and loneliness with heart disease, and our targeted analysis of CAD revealed that patients with polygenic scores in the highest decile for either MDD or loneliness had a more than 50% greater risk of CAD compared with patients with scores in the lowest decile. Conversely, a polygenic score for CAD was not associated with MDD or other psychiatric phenotypes, in accordance with a previous study of the UK biobank population [35]. Epidemiological associations between MDD and loneliness and heart disease are known [36]; here we showed that the association is partly attributable to genetics. Similar results were observed in ARIC participants, who were prospectively surveyed for heart disease outcomes using traditional epidemiological approaches.
