Our fifth aim was to replicate our findings in an independent population. The ARIC sample included 7197 participants of European ancestry with clean genotyping data, followed for a median of 16.0 years (range 0.05–18.1), over which time 923 incident CAD cases were recorded (Supplementary Table 7). The polygenic score for MDD was associated with a hazard ratio (HR) of 1.07 (95% CI, 0.99–1.14; P = 0.07), as was the polygenic score for loneliness (HR, 1.07 [95% CI, 1.01–1.15]; P = 0.03). Associations were robust to confounder adjustment in females but not in males (Supplementary Fig. 6), and the polygenic score for loneliness|MDD was associated with a CAD HR of 1.14 (95% CI, 1.01–1.29; P = 0.02) in females versus 0.98 (95% CI, 1.02–1.29; P = 0.60) in males in the fully adjusted model (interaction P < 0.05).
