Mendelian randomization study on the causal effects of glioma on Alzheimer's disease

Abstract Background Previous observational studies have revealed an inverse relationship where cancer patients have a reduced risk to develop Alzheimer’s disease (AD) and vice versa. The present two-sample Mendelian randomization (MR) study aims to identify the causal link between gliomas and AD. Methods The largest gliomas genome-wide association study (GWAS) was used. A previously reported AD GWAS (24,087 cases and 55,058 controls from European ancestry) was used to assess the effect of gliomas on AD. MR-egger_intercept and MR_egger and inverse variance weighted (IVW) in Cochran’s Q-test were used to determine the pleiotropy and heterogeneity, respectively. IVW and weighted median were used to perform MR analysis. Finally, the effect of a single nucleotide polymorphism (SNP) was used to test the SNP bias. Results We did not find a significant pleiotropy or heterogeneity of all three gliomas genetic instrumental variants (IVs) in AD GWAS. Interestingly, we found that as gliomas genetically increased, the risk of AD increased using IVW (odds ratio [OR] = 1.0167, 95% confidence interval [CI] = 1.0079–1.0257, p = 0.0002). This was further proven by weighted median (OR = 1.0161, 95% CI = 1.0058–1.0267, p = 0.0023). Reverse MR analysis shows no causal effect of AD on gliomas. Conclusions Our analysis suggested a causal link between genetically increased gliomas and the increased risk of AD in European ancestries. Thus, gliomas may be a risk factor for AD.