Exploring metabolite-mediated links between lipidome and deep vein thrombosis: Insights from Mendelian randomization analysis

The aim was to investigate the causal relationship between the lipidome and deep vein thrombosis (DVT) while identifying and quantifying the role of metabolites as potential mediators. Two-sample Mendelian randomization (MR) analysis of lipid species (n = 7174) and DVT (6767 cases and 330,392 controls) was performed using pooled data from genome-wide association studies. In addition, we quantified the proportion of metabolite-mediated lipidomic effects on DVT using 2-step MR. Phosphatidylcholine (18:0_18:2) levels mined from 179 lipids using MR analysis reduced the risk of DVT (odds ratio [OR]: 0.997; 95% CI: 0.996-0.999; P = 4.25 × 10-4; false discovery rate [FDR] = 0.013). Octadecadienedioate (C18:2-DC) levels increased with the increasing phosphatidylcholine (18:0_18:2) levels (OR: 1.087, 95% confidence interval [CI]: [1.024, 1.154], P = .006). Octadecadienedioate (C18:2-DC) levels mined from 1400 metabolites using MR analysis reduced the DVT risk (OR: 0.997; 95% CI: [0.996, 0.999], P = 6.11 × 10-6; FDR = 8.55 × 10-3). The proportion of the predicted genes for phosphatidylcholine (18:0_18:2) levels mediated by octadecadienedioate (C18:2-DC) levels was 7.8%. This study identified octadecadienedioate (C18:2-DC) levels as a potential mediator of the causal relationship between phosphatidylcholine (18:0_18:2) levels and DVT, which provides direction for the future investigation of DVT; however, further research on other potential mediators is still needed.