Somatic Mutations in Cardiovascular Disease

Advances in population-scale genomic sequencing have greatly expanded the understanding of the inherited basis of cardiovascular disease (CVD). Reanalysis of these genomic datasets identified an unexpected risk factor for CVD, somatically acquired DNA mutations. In this review, we provide an overview of somatic mutations and their contributions to CVD. We focus on the most common and well-described manifestation, clonal hematopoiesis of indeterminate potential. We also review the currently available data regarding how somatic mutations lead to tissue mosaicism in various forms of CVD, including atrial fibrillation and aortic aneurism associated with Marfan Syndrome. Finally, we highlight future research directions given current knowledge gaps and consider how technological advances will enhance the discovery of somatic mutations in CVD and management of patients with somatic mutations.

Automated summary

Advances in genomic sequencing have increased our understanding of the inherited basis of cardiovascular disease (CVD). Reanalysis of genomic datasets revealed somatically acquired DNA mutations as an unexpected risk factor for CVD. This review provides an overview of somatic mutations and their contributions to CVD, focusing on the most common manifestation of clonal hematopoiesis. The available data on how somatic mutations lead to tissue mosaicism in various forms of CVD are also reviewed, along with future research directions and technological advances.