Fig. 1.

Results from large-scale genome-wide association studies (GWAS) of major depressive disorder (MDD) [11], loneliness [10], and coronary artery disease (CAD) [12] can be used in disentangle relationships between the three traits. a Genome-wide genetic correlations show that all three traits share some genetic risk factors. b Mendelian randomization experiments using the top associations from GWAS as genetic instruments found no causal effect of CAD on MDD on loneliness, while the reverse tests were likely under-powered. c This study used polygenic scores for MDD and loneliness in electronic health records linked to DNA samples and found pleiotropic relationships between MDD, loneliness, and CAD even after accounting for comorbidities and conventional heart disease risk factors