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.
| Original language | German |
|---|---|
| Pages (from-to) | 1-6 |
| Number of pages | 6 |
| Journal | Zeitschrift fur Rheumatologie |
| DOIs | |
| Publication status | Accepted/In press - 2018 Jul 5 |
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Keywords
- Alzheimer’s disease
- Causal association
- Mendelian randomization
- Rheumatoid arthritis
- Susceptibility
ASJC Scopus subject areas
- Rheumatology
Cite this
Kausalzusammenhang zwischen rheumatoider Arthritis und vermindertem Risiko für M. Alzheimer : Eine Mendel-Randomisierungsstudie. / Bae, S. C.; Lee, Young Ho.
In: Zeitschrift fur Rheumatologie, 05.07.2018, p. 1-6.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Kausalzusammenhang zwischen rheumatoider Arthritis und vermindertem Risiko für M. Alzheimer
T2 - Eine Mendel-Randomisierungsstudie
AU - Bae, S. C.
AU - Lee, Young Ho
PY - 2018/7/5
Y1 - 2018/7/5
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Causal association
KW - Mendelian randomization
KW - Rheumatoid arthritis
KW - Susceptibility
UR - http://www.scopus.com/inward/record.url?scp=85049568206&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049568206&partnerID=8YFLogxK
U2 - 10.1007/s00393-018-0504-8
DO - 10.1007/s00393-018-0504-8
M3 - Article
C2 - 29974225
AN - SCOPUS:85049568206
SP - 1
EP - 6
JO - Zeitschrift fur Rheumatologie
JF - Zeitschrift fur Rheumatologie
SN - 0340-1855
ER -