Kausalzusammenhang zwischen rheumatoider Arthritis und vermindertem Risiko für M. Alzheimer: Eine Mendel-Randomisierungsstudie

Objective: This study aimed to examine whether rheumatoid arthritis (RA) is causally associated with Alzheimer’s disease (AD). Methods: We performed a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. We used the publicly available summary statistics datasets from three-stage trans-ethnic genome-wide association studies (GWAS) meta-analyses of 29,880 RA cases and 73,758 controls as exposures and a meta-analysis of 4 GWAS datasets consisting of 17,008 AD cases and 37,154 controls of European descent as outcomes. Results: We selected 80 single nucleotide polymorphisms (SNPs) from GWAS data on RA as instrumental variables (IVs), 60 of which were associated with RA on a genome-wide significance level. The IVW method showed evidence to support an inverse causal association between RA and AD (β?= −0.039, standard error [SE]?= 0.017, P?= 0.021). MR-Egger regression revealed that directional pleiotropy was unlikely to be a source of bias in the results (intercept?= 0.002; P?= 0.649). The MR-Egger analysis showed no causal association between RA and AD (β?= −0.050, SE?= 0.030, P?= 0.096). However, the weighted median approach showed that RA and AD were causally linked (β?= −0.078, SE?= 0.024, P?= 0.001). The funnel plot did not show heterogeneity between IV estimates based on the individual variants. Conclusions: The MR analysis supports that RA was causally associated with a reduced risk of AD.