Abstract
AbstractAbdominal aortic aneurysm has a high heritability and often co-occurs with other cardiometabolic disorders, suggesting shared genetic susceptibility. We investigate this commonality leveraging recent GWAS studies of abdominal aortic aneurysm and 32 cardiometabolic traits. We find significant genetic correlations between abdominal aortic aneurysm and 21 of the cardiometabolic traits investigated, including causal relationships with coronary artery disease, hypertension, lipid traits, and blood pressure. For each trait pair, we identify shared causal variants, genes, and pathways, revealing that cholesterol metabolism and inflammation are shared most prominently. Additionally, we show the tissue and cell type specificity in the shared signals, with strong enrichment across traits in the liver, arteries, adipose tissues, macrophages, adipocytes, and fibroblasts. Finally, we leverage drug-gene databases to identify several lipid-lowering drugs and antioxidants with high potential to treat abdominal aortic aneurysm with comorbidities. Our study provides insight into the shared genetic mechanism between abdominal aortic aneurysm and cardiometabolic traits, and identifies potential targets for pharmacological intervention.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Reference113 articles.
1. Song, P. et al. The global and regional prevalence of abdominal aortic aneurysms: a systematic review and modeling analysis. Ann. Surg. 277, 912–919 (2023).
2. Aggarwal, S., Qamar, A., Sharma, V. & Sharma, A. Abdominal aortic aneurysm: a comprehensive review. Exp. Clin. Cardiol. 16, 11–15 (2011).
3. Reimerink, J. J., van der Laan, M. J., Koelemay, M. J., Balm, R. & Legemate, D. A. Systematic review and meta-analysis of population-based mortality from ruptured abdominal aortic aneurysm. Br. J. Surg. 100, 1405–1413 (2013).
4. Golledge, J., Thanigaimani, S., Powell, J. T. & Tsao, P. S. Pathogenesis and management of abdominal aortic aneurysm. Eur. heart J. 44, 2682–2697 (2023).
5. Qian, G., Adeyanju, O., Olajuyin, A. & Guo, X. Abdominal aortic aneurysm formation with a focus on vascular smooth muscle cells. Life (Basel, Switz.) 12, 191 (2022).