Causal Associations Between Human Blood Metabolites and Cardio-Cerebrovascular Diseases: A Mendelian Randomisation Study

BackgroundBlood metabolites are crucial in various aspects of human health. However, current evidence regarding the role of circulating metabolites in various cardio-cerebrovascular diseases (CVDs) is limited. Mendelian randomisation (MR) can be used to provide information about these metabolites.ObjectivesOur primary aim was to investigate the causal relations between human blood metabolites and the risk of 10 CVDs.MethodsWe conducted a two-sample MR study. Data on 486 human blood metabolites were obtained from a genome-wide association study (GWAS) involving 7824 participants. Outcome data were sourced from the most recent large-scale GWAS meta-analysis by FinnGen (R9) on various CVDs. The inverse variance-weighted (IVW) model was used as the primary method for this analysis. Moreover, we performed sensitivity analyses, which included heterogeneity testing, horizontal pleiotropy testing and leave-one-out analysis, to evaluate the robustness and credibility of the findings.ResultsThis study identified 36 known metabolites potentially associated with 10 CVDs, and sensitivity analyses showed no significant heterogeneity or pleiotropy.ConclusionsOur study utilised systematic MR analyses and provides evidence for the causal relations between blood metabolites and CVDs. This sheds new light on the potential mechanisms underlying various CVDs and holds significant implications for screening, preventing and treating these conditions.