Since a complicated picture has emerged on the association of ACE2 effects on cardiovascular physiology in the COVID-19 pandemic, we hypothesized that dissection of the cardiac genetic regulatory network of ACE2 using a systems genetics approach would uncover the underlying genetic determinants in ACE2-driven cardiovascular function, the results of which would benefit in the diagnosis and care of patients with cardiovascular disease, including cardiovascular complications in COVID-19. This evidence concerns the gene ACE2 and cardiovascular disorder.