Association between human blood metabolome and the risk of coronary heart disease: Mendelian randomization study

Abstract

In this study, we employed Mendelian Randomization (MR) to elucidate the causal relationships between specific blood metabolites and Coronary Heart Disease (CHD). By analyzing data from Genome-Wide Association Studies (GWAS) and the FinnGen database, we conducted a two-sample MR analysis focusing on 40 metabolites and 6 metabolite ratios linked to CHD risk. Our findings highlight a group of metabolites significantly influencing CHD risk, either augmenting or mitigating it. Rigorous sensitivity checks, including MR-Egger and MR-PRESSO, negated the influence of horizontal pleiotropy and reinforced the robustness of our results. Furthermore, reverse MR analysis unveiled a bidirectional influence between certain metabolites and CHD, suggesting a complex mutual interaction. This study not only unravels intricate connections between metabolites and CHD, but also paves the way for potential biomarkers instrumental in CHD prevention and therapy. However, it acknowledges certain limitations, such as the modest sample size and a primary focus on European genetic data, underscoring the need for further investigations in more diverse population cohorts.