Supplementary Material for: The Causal Relationship between Lipid Metabolites and Multiple Myeloma Risk: A Mendelian Randomization Study

Introduction: Research has demonstrated a potential link between lipid metabolites and multiple myeloma (MM); however, the causal relationship remains uncertain. This Mendelian randomization (MR) study aimed to explore the potential causal relationship between lipid metabolites and MM. Methods: In this study, data on lipid metabolites were obtained from a genome-wide association study of metabolites in blood samples from 7,824 Europeans. Genetic information related to MM came from the UK Biobank database, encompassing 601 patients with MM and 372,016 control samples. In this MR analysis, inverse-variance weighted method was used as the primary analysis method; MR Egger and weighted median were employed as complementary approaches. Sensitivity analyses were conducted using the Cochran Q test, MR-Egger intercept, MR-PRESSO, and leave-one-out analysis. Results: A total of 121 human lipid metabolites were analyzed in this MR study. The analysis result revealed that 1-docosahexaenoyl-glycerophosphocholine [odds ratio (OR) = 1.0059, 95% confidence interval (CI) 1.0043–1.0076, P < 0.01 , FDR = 0.12], tetradecanedioate (OR = 1.0007, 95% CI 1–1.0013, P = 0.0498 , FDR = 0.23), and X-12990-docosapentaenoic acid (OR = 1.0029, 95% CI 1.0015–1.0044, P < 0.01 , FDR = 0.15) were linked to an increased risk of MM. As for palmitoleate (OR = 0.9972, 95% CI 0.9947–0.9997, P = 0.0299 , FDR = 0.19) , a nominal inverse association was observed. None of these associations reached statistical significance after FDR correction (all FDR > 0.05). Sensitivity analyses verified the robustness of these nominally significant results. Conclusion: Genetic evidence demonstrated nominal associations of 1-docosahexaenoyl-sn-glycero-3-phosphocholine, tetradecanedioate, X-12990-eicosapentaenoic acid, and palmitoleate with MM risk, though these did not survive FDR correction. While these findings suggest potential metabolic pathways in MM pathogenesis, further validation is required before considering these compounds as biomarkers for clinical screening or drug target selection.