Exploring the Genetic Architecture of Spontaneous Coronary Artery Dissection Using Whole-Genome Sequencing

Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome that predominantly affects women. Its pathophysiology remains unclear, but connective tissue disorders (CTD) and other vasculopathy have been observed in many SCAD patients. A genetic component for SCAD is increasingly appreciated, although few genes have been robustly implicated. We sought to clarify the genetic cause of SCAD using targeted and genome-wide methods in a cohort of sporadic cases to identify both common and rare disease-associated variants. SCAD shares some genetic overlap with CTD, even in the absence of any significant CTD phenotype. Consistent with a complex genetic architecture, SCAD patients also have a higher burden of common variants than controls.