Exploring the causal relationship between B lymphocytes and Parkinson’s disease: a bidirectional, two-sample Mendelian randomization study

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder with extensive involvement of motor symptoms, imposing a heavy economic burden on patients and society. B lymphocytes, a group of immune cells associated with humoral immunity, have been shown to be involved in the pathogenesis of PD. However, the causal relationship and potential pathogenic effects of B cell in PD remain unclear. Based on the three core hypotheses of the Mendelian randomization (MR) study, we explored causal associations between 190 B-cell immunological traits and 482,730 European individuals (Ncase = 33,674, Ncontrol = 449,056) from genome wide association studies by means of the two-sample bidirectional MR method. The inverse‑variance weighted method was selected as the main approach when conducting MR analysis. Finally, the results were verified by the heterogeneity and horizontal pleiotropy analyses. Five B-cell immunological phenotypes were nominally associated with PD at the significance threshold of P < 0.05. Concretely, IgD + CD38− B cell %lymphocyte (OR 1.052, 95% CI 1.001–1.106, P = 0.046), CD20 on IgD− CD24− B cell (OR 1.060, 95% CI 1.005–1.117, P = 0.032), CD38 on IgD+ CD24− B cell (OR 1.113, 95% CI 1.028–1.206, P = 0.009), and BAFF-R on CD20− B cell (OR 1.093, 95% CI 1.010–1.184, P = 0.027) were identified as risk factors for PD. Instead, CD38 on Plasma Blast-Plasma Cell (OR 0.894, 95% CI 0.802–0.996, P = 0.043) was proved to be protective. However, there is no statistically significant correlation between B cell and PD after Bonferroni correction. The results of reverse MR were negative, avoiding the reverse causal effects. Eventually, the association results were identified as stable across several sensitivity analyses. Briefly, our study might demonstrate the key factor of B cells in PD. Further studies are warranted to clarify the associations for early identification and immunotherapeutic development in PD patients.