Plasma proteins and coronary atherosclerosis: A Mendelian randomization study

Coronary atherosclerosis (AS) is a complicated and severe chronic pathological process that contributes to the basis of various cardiovascular diseases, which causes a serious challenge to the global healthcare system. AS is the underlying physiopathological mechanism. Despite recent advances in the research of biomarkers and therapeutic targets for AS, there remain significant limitations in the current targeted therapies for AS. This study utilizes Mendelian randomization analysis to leverage genetic variations in order to identify plasma proteins with causal relationships to coronary AS. Utilizing publicly available genome-wide association study datasets, 4907 plasma proteins were assessed as exposure factors, with coronary AS being the outcome variable. The primary analytical method employed was the inverse variance weighted approach to ensure the robustness and accuracy of the causal relationships. In addition, to verify the reliability of the results, we employed several complementary methods, including the weighted median, Mendelian randomization-Egger, weighted mode, and simple mode approaches, to thoroughly assess the heterogeneity and pleiotropy of the findings. To ensure the robustness of the results and to exclude potential biases, a leave-one-out sensitivity analysis was performed. Twenty potential therapeutic targets were analyzed and identified (P < .05), combined with multiple bioinformatic analyses; among them, fibronectin 1 was identified as a key target. These findings may provide a new theoretical basis for future research in coronary AS drug development and therapeutic strategies.