Association between human blood metabolome and risk of myocarditis: a Mendelian randomization study

Abstract

Objective Myocarditis is a common disease of the cardiovascular and immune systems, but the relationship between relevant metabolites in the blood and the risk of myocarditis has not been established. To identify biometabolic markers in myocarditis blood, we performed a two-sample MR study. Methods MR preliminary analysis: based mainly on the results of IVW, supplemented by MR-Egger, weighted median, and weighted mode for FDR multiple correction; removal of confounders: screened on the GWAS Catalog website; sensitivity analyses: Cochrane Q-test, Egger regression, MR- PRESSO, scatterplot, funnel plot, forest plot; Genetic and directional analysis: co-localization analysis, steiger test; Replicative and Meta-analysis: meta-analysis by extracting the same ending GWAS from another database. Results MR analysis identified significant correlations after FDR for 5 metabolic biomarkers (P < 0.05). Four known metabolites: kynurenine, 1-stearoyl-GPE (18:0), Deoxycarnitine, 5-acetylamino-6-formylamino-3-methyluracil with one unknown metabolite: X-25422. Among them, kynurenine (OR = 1.441, 95%CI = 1.089–1.906, P = 0.018) and 1-stearoyl-GPE (18:0) (OR = 1.263, 95%CI = 1.029–1.550, P = 0.029) were risk factors for myocarditis, Deoxycarnitine (OR = 0.813, 95%CI = 0.676–0.979, P = 0.029), 5-acetylamino-6-formylamino-3-methyluracil (OR = 0.864, 95%CI = 0.775–0.962, P = 0.018) and X-25422 (OR = 0.721, 95%CI = 0.587–0.886, P = 0.009) were protective factors against myocarditis. There was no heterogeneity, horizontal pleiotropy, or sensitivity (P < 0.05), no shared genetic factors between exposure and outcome, and the causality was in the right direction. Meta-analysis results again identified five metabolites causally related to myocarditis (I² < 50%, P < 0.05). Conclusion This study identified a causal relationship between five circulating metabolites and myocarditis, and Kynurenine, 1-stearoyl-GPE (18:0), Deoxycarnitine, X-25422, and 5-acetylamino-6-formylamino-3-methyluracil may be as potential drug targets for myocarditis, providing a theoretical basis for the prevention, diagnosis, and treatment of myocarditis.