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Causal association between rheumatoid arthritis and a decreased risk of Alzheimer's disease : A Mendelian
1Department of Rheumatology, Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea (Republic of).
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.