Rheumatoid arthritis is a protective factor against Alzheimer’s disease: a bidirectional two-sample Mendelian randomization study

Background Epidemiological evidence suggests that there is an association between rheumatoid arthritis (RA) and Alzheimer’s disease (AD). However, the causal relationship between RA and AD remains unclear. Therefore, this study aimed to investigate the causal relationship between RA and AD. Methods Using publicly available genome-wide association study datasets, bidirectional two-sample Mendelian randomization (TSMR) was performed using the inverse-variance weighted (IVW), weighted median, MR‒Egger regression, simple mode, and weighted mode methods. Results The results of MR for the causal effect of RA on AD (IVW, odds ratio [OR] = 0.959, 95% confidence interval [CI]: 0.941–0.978, P = 2.752E-05; weighted median, OR = 0.960, 95% CI: 0.937–0.984, P = 0.001) revealed a causal association between genetic susceptibility to RA and an increased risk of AD. The results of MR for the causal effect of AD on RA (IVW, OR = 0.978, 95% CI: 0.906–1.056, P = 0.576; weighted median, OR = 0.966, 95% CI: 0.894–1.043, P = 0.382) indicated that there was no causal association between genetic susceptibility to AD and an increased risk of RA. Conclusions The results of this two-way two-sample Mendelian randomization analysis revealed a causal association between genetic susceptibility to RA and a reduced risk of AD but did not reveal a causal association between genetic susceptibility to AD and an increased or reduced risk of RA.