This study included five aims. The first was to identify the medical morbidity patterns associated with polygenic scores for MDD and loneliness in the Vanderbilt University Medical Center (VUMC) EHR and accompanying biobank, BioVU. Second, we undertook a targeted analysis of CAD, and determined whether genetic risk for MDD and loneliness remained associated with CAD in the absence of a clinical diagnosis of MDD. Third, we examined whether the risk of CAD conferred by MDD and loneliness risk scores could be attenuated by accounting for multiple conventional CAD risk factors. Fourth, given the well-established sex differences in MDD incidence [1], and in CAD mortality, presentation, and risk factors [13–15], we repeated all analyses in males and females separately. Fifth, we replicated our findings in a large prospectively collected population cohort, the Atherosclerosis Risk in Communities (ARIC) study. Our results provided strong evidence that pleiotropic risk factors for MDD and loneliness increase the risk of CAD, with more pronounced effects in females than in males.
