Shuai Yuan

The abdominal aorta, a significant blood vessel in our body, can vary in size due to genetic and environmental factors. For some individuals, this vessel may enlarge excessively, leading to a life-threatening condition known as an abdominal aortic aneurysm. If it ruptures, the consequences are often fatal. Despite the gravity of this condition, our predictive and non-surgical treatment capabilities are limited. The genome-wide association study (GWAS) technique offers a pathway to identify genes associated with specific diseases. While several GWASs have explored genes related to abdominal aortic aneurysms, the genetic determinants of a typical aorta's size remain under-researched due to the confined power. In this project, we plan to conduct a de novo GWAS using data from the VA Million Veteran Program, the Penn Medicine Biobank, the United Kingdom Small Aneurysm Growth Study, the UK Biobank study, and the CHARGE consortium, resulting in an aggregate sample size of ~167,000 individuals with imaging and genetic data. The project's primary objective is to unravel the pathogenesis of abdominal aortic aneurysms by discerning the genetic intersections and disparities between normal abdominal aortic diameters and their extreme counterparts. By completing this analysis, our research will shine a light on specific genes and pathways influencing aortic size, helping elucidate how they contribute to the development of normal aorta to aortic aneurysms. This knowledge will subsequently guide efforts in prevention and therapeutic strategies for abdominal aortic aneurysms. Moreover, an enlarged aorta often goes unnoticed because it typically does not manifest any immediate symptoms, making early detection of potential aortic aneurysms challenging. While widespread imaging is infeasible, there is an escalating focus on discerning characteristics of individuals exhibiting abdominal aorta size enlargement. In this project, we also aim to create and refine a clinical risk assessment tool designed to accurately predict the size of the aorta and the propensity for abdominal aortic aneurysms. By integrating genetic markers into this predictive framework, we aim to enhance its precision. Ultimately, our findings will pave the way for timely detection and intervention strategies, offering a proactive approach to managing and preventing aortic aneurysms.