Abstract
The causal association between the autoimmune disease and the development of glioma and its subtypes remains unclear. We performed a comprehensive Mendelian randomization (MR) to clarify their causal association from genetic perspective. We obtained the summary-level datasets for autoimmune diseases from recently published genome-wide association studies in the UK Biobank (UKB) and the FinnGen consortium. Additionally, we collected summary statistics datasets related to glioma and its subtypes from a comprehensive meta-analysis genome-wide association study, which included 12,488 cases and 18,169 controls. We primarily used inverse variance weighting method, supplemented by Bonferroni correction to account for multiple tests to reduce the probability of false positive results. We also performed sensitivity analyses to address potential pleiotropy and strengthen the reliability of the results. After meta-analysis, pernicious anemia may decrease the risk of glioblastoma (GBM) (UKB: odds ratio (OR) = 0.01, 95% confidence interval (CI) = 0.01-0.02, P = 1.01E-12; FinnGen: OR = 0.86, 95% CI = 0.79-0.93, P = .0002; Meta: OR = 0.04, 95% CI = 0.03-0.04). In reverse MR analysis, GBM decreased the risk of celiac disease (UKB: OR = 0.96, 95% CI = 0.95-0.98, P = .0000; FinnGen: OR = 0.89, 95% CI = 0.84-0.94, P = .0001; Meta: OR = 0.95, 95% CI = 0.94-0.97). Heterogeneity and pleiotropy analyses, and reverse analysis, confirmed the robustness of these results. From the genetic perspective, our MR study uncovered that pernicious anemia may decrease the risk of GBM. Conversely, GBM appeared to mitigate the risk of celiac disease. Future studies are required to validate the causal association and illuminate the underlying mechanisms.