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Z Rheumatol. 2019 May;78(4):359-364. doi: 10.1007/s00393-018-0504-8.

Causal association between rheumatoid arthritis and a decreased risk of Alzheimer's disease : A Mendelian randomization study.

Author information

1
Department of Rheumatology, Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea (Republic of).
2
Department of Rheumatology, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, 02841, Seoul, Korea (Republic of). lyhcgh@korea.ac.kr.

Abstract

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.

KEYWORDS:

Alzheimer’s disease; Causal association; Mendelian randomization; Rheumatoid arthritis; Susceptibility

PMID:
29974225
DOI:
10.1007/s00393-018-0504-8

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