Mendelian randomization identified 12 plasma protein ratios with significant causal associations with aneurysms, potentially mediated by blood pressure and lipids.
Observational
Do genetically predicted plasma protein-to-protein ratios have a causal effect on the risk of aneurysms?
This Mendelian Randomization study identified 12 plasma protein ratios causally associated with aneurysms, suggesting potential new therapeutic targets involving anti-inflammatory and lipid-lowering pathways.
INTRODUCTION: Proteomics research provides significant insights for the diagnosis and treatment of diseases. Protein ratios reflect biological connections between related proteins and can help identify clinically relevant loci. Exploring the relationship between plasma protein-to-protein ratios and aneurysms may help identify new targets for prevention and treatment. METHODS: We performed a two-sample Mendelian Randomization (MR) analysis to assess the associations between 2,821 protein ratios and various types of aneurysms. Twostep MR was utilized to investigate the potential mediating role of cardiometabolic factors. Through pathway enrichment analysis and drug target evaluation, we further elucidated the potential mechanisms and therapeutic targets related to aneurysms. RESULTS: After MR analysis, we identified 12 protein ratios with significant causal associations with aneurysms. Among them, seven protein ratios were associated with Thoracic Aortic Aneurysms (TAA), three with Aortic Aneurysms (AA), one with Abdominal Aortic Aneurysms (AAA), and one with Subarachnoid Hemorrhage (SAH). No significant causal associations were identified for unruptured intracranial aneurysm. We further performed a two-step MR analysis and found associations between cardiometabolic traits like blood pressure and lipids with aneurysms, confirming their potential mediating roles between protein ratios and aneurysms. Lastly, our drug target evaluation suggested that anti-inflammatory and lipid-lowering drugs are associated with aneurysm-related protein ratios. DISCUSSION: We identified 12 plasma protein ratios significantly associated with aneurysms, with blood pressure and lipids potentially mediating these associations. Additionally, our findings suggest that anti-inflammatory and lipid-lowering drugs are associated with the 12 plasma protein ratios, offering new insights for the treatment of aneurysms. CONCLUSIONS: Our findings elucidate the significant associations between 12 plasma protein ratios and aneurysms. These results provide new perspectives for the prevention and management of aneurysms.
Yin et al. (Tue,) conducted a observational in Aneurysms. Plasma protein-to-protein ratios was evaluated on Causal associations with aneurysms. Mendelian randomization identified 12 plasma protein ratios with significant causal associations with aneurysms, potentially mediated by blood pressure and lipids.