Causal relationship between branched-chain amino acids and peripheral atherosclerosisï¼ a Mendelian randomization study
Journal Title: Shanghai Journal of Preventive Medicine - Year 2023, Vol 35, Issue 6
Abstract
ObjectiveWe conducted a two-sample Mendelian randomization ï¼MRï¼ study to assess the causal relationship between circulating isoleucineï¼ leucine and valine levels and the risk of peripheral atherosclerosis.MethodsBased on the large-scale genome-wide association study ï¼GWASï¼ databaseï¼ single nucleotide polymorphisms ï¼SNPsï¼ closely related to the circulating levels of isoleucineï¼ leucine and valine were identified as instrumental variables ï¼IVsï¼. Two-sample MR analysis applying the inverse variance weighted ï¼IVWï¼ method and the weighted median estimator ï¼WMEï¼ 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 methodï¼ and the leave-one-out method was used in sensitivity analysis.ResultsFourï¼ one and one SNPs were identified as IVs for circulating isoleucineï¼ leucine and valine levelsï¼ respectively. For isoleucineï¼ the IVW model demonstrated there was no evidence of heterogeneity among the IVs ï¼P=0.715ï¼ï¼ and there was a significant causal relationship between the increase of circulating isoleucine level and a higher risk of peripheral atherosclerosis risk. Per every 1 elevated standard deviation ï¼SDï¼ of circulating isoleucine level resulted in increasing 31% of peripheral atherosclerosis risk ï¼OR=1.31ï¼ 95%CIï¼ 1.07â1.61ï¼. Similarlyï¼ the ORï¼95%CIï¼ was 1.33 ï¼1.04â1.71ï¼ in the WME model. The MR-Egger regression and MR-PRESSO analysis indicated no evidence of pleiotropy in IVs ï¼all P>0.05ï¼. The result of the leave-one-out sensitivity analysis was stable. The Wald ratio model displayed that the causal relationship between circulating leucine and valine levels and the risk of peripheral atherosclerosis was not statistically significant. The OR ï¼95%CIï¼ for leucine and valine was 1.13 ï¼0.78â1.63ï¼ and 1.11 ï¼0.82â1.50ï¼ï¼ respectively.ConclusionThere is a significant causal relationship between the increase of circulating isoleucine level and a higher peripheral atherosclerosis risk. The causal relationships between circulating leucine and valine levels and the risk of peripheral atherosclerosis need to be further confirmed in future studies.
Authors and Affiliations
FU Yuanyuan,CHEN Jie,CAI Shiyuan,LI Xue,
Keywords
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