Multiple Sclerosis and Hematologic Malignancies: A Bidirectional Mendelian Randomization Study

Observational studies have reported associations between multiple sclerosis (MS) and hematologic malignancies (HM), but findings remain inconsistent. We conducted a bidirectional two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association summary statistics for MS (n = 115,803) and HM (n = 218,792). Primary causal estimates were obtained with the inverse-variance-weighted (IVW) estimator, complemented by prespecified sensitivity analyses for heterogeneity and pleiotropy. Genetically proxied liability to MS was associated with higher odds of leukemia (unspecified subtype) (odds ratio [OR] 1.311, 95% confidence interval [CI] 1.002-1.716, P = 0.048) and Hodgkin lymphoma (HL) (OR 1.224, 95% CI 1.052-1.425, P = 0.009), with no evidence for other leukemia, lymphoma, or plasma-cell neoplasm subtypes (all P > 0.05). Tests indicated no substantial heterogeneity or directional pleiotropy for the leukemia (unspecified subtype) or HL analyses. These results provide genetic evidence consistent with an elevated risk of select HM subtypes among individuals with higher genetic liability to MS; however, the signals should be interpreted cautiously and validated in larger, multi-ancestry datasets and with additional causal frameworks.