Objective To explore the causal relationship between metabolites and varicose veins using Mendelian randomization.

Methods In the genome-wide association study (GWAS) database, 1400 metabolites associated with human diseases were chosen as the exposure factors, and the varicose veins were considered as the outcome. The inverse variance weighting (IVW), MR-Egger regression, weighted median method (WME), weighted mode method and simple mode method were used to perform two sample Mendelian randomization, and the causal relationship between 1400 human disease-related metabolites and varicosity was evaluated by the outcome.

Results After FDR correction, 8 metabolites associated with varicose veins were identified in this study, which included the isovalerylcarnitine (C5) (OR = 1.15, 95%CI = 1.06–1.25, P = 0.0007108547, FDR = 0.137), alpha-pregnan-3beta, 20 alpha-diolmonosulfate (2) (OR = 0.92, 95%CI = 0.87–0.97, P = 0.0011590031, FDR = 0.195), pregnenetrioldisulfate (OR = 1.04, 95%CI = 1.02–1.07, P = 0.0007029416, FDR = 0.137), N2-acetyl, N6, N6-dimet-hyllysine (OR = 1.08, 95%CI = 1.03–1.12, P = 0.0002221230, FDR = 0.06), propionylcarnitine (C3) (OR = 1.17, 95%CI = 1.10–1.25, P = 7.936197 × 10^–7, FDR = 0.001), myristoylcarnitine (C14) (OR = 1.26, 95%CI = 1.12–1.41, P = 7.247852 × 10^–5, FDR = 0.024), acetylphenylalanine (OR = 1.09, 95%CI = 1.05–1.13, P = 1.535730 × 10^–5, FDR = 0.007) and phosphate/tyrosine (OR = 0.86, 95%CI = 0.80–0.92, P = 1.518885 × 10^–5, FDR = 0.007).

Conclusions This study proves that there is a close relationship between metabolites and varicose veins at the genetic level, which provides a new idea for future clinical research.