Genome-wide Cross-multi-trait Analysis into Shared Genetic Architecture of Coronary Artery Disease and Aortic Aneurysms

While affecting distinct vascular territories, coronary artery disease, abdominal aortic aneurysms and thoracic aortic aneurysms share similar risk factors and pathophysiological resemblance. To identify novel pleiotropic and heterogenous loci, we performed a joint meta-analysis leveraging the shared genetic architecture of thereof. Using summary statistics from three independent genome-wide association studies, we perform nine separate multivariate genome-wide scans together with cross-trait validation and identify 59 regions previously unreported as genome-wide significant for their respective traits. In our downstream investigations, we comprehensively map the functional characteristics of the loci, revealing common patterns of enriched cell types and tissues, prominent cellular pathways, expression quantitative loci and genetic correlation. Findings from this study support the presence of cardiovascular polygenicity, identify novel genome-wide significant variants for coronary artery disease and aortic aneurysms, and extend the previous knowledge on their genetic overlap and relationship. Taken together, these results show that joint analysis of related atherosclerotic disease traits allows for identification of unified biology that may offer the opportunity for future therapeutic manipulation.