biostudies-literatureZheng SNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (National Science Foundation of China)5652https://www.ebi.ac.uk/biostudies/studies/S-EPMC11226445biostudies-literatureUnknown15(1)Abdominal 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.Nature communicationsAbdominal aortic aneurysm and cardiometabolic traits share strong genetic susceptibility to lipid metabolism and inflammation.PMC1122644532270626Tsao PSPan CZheng SfalseAbdominal aortic aneurysm and cardiometabolic traits share strong genetic susceptibility to lipid metabolism and inflammation.Abdominal 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.2024-01-01T00:00:00Z2024 Jul2025-04-22T15:36:11.171Z2025-04-06T01:24:25.763ZS-EPMC112264453896965910.1038/s41467-024-49921-7