Causal relationship between branched-chain amino acids and peripheral atherosclerosis： a Mendelian randomization study

ObjectiveWe conducted a two-sample Mendelian randomization （MR） study to assess the causal relationship between circulating isoleucine， leucine and valine levels and the risk of peripheral atherosclerosis.MethodsBased on the large-scale genome-wide association study （GWAS） database， single nucleotide polymorphisms （SNPs） closely related to the circulating levels of isoleucine， leucine and valine were identified as instrumental variables （IVs）. Two-sample MR analysis applying the inverse variance weighted （IVW） method and the weighted median estimator （WME） method were performed to estimate the causal relationship between the risk of peripheral atherosclerosis and the exposure with more than three SNPs that were available as IVs. The pleiotropy was evaluated by using the MR-Egger regression and MR-PRESSO method， and the leave-one-out method was used in sensitivity analysis.ResultsFour， one and one SNPs were identified as IVs for circulating isoleucine， leucine and valine levels， respectively. For isoleucine， t