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

Translated title of the contribution: Causal association between rheumatoid arthritis and a decreased risk of Alzheimer’s disease: A Mendelian randomization study

S. C. Bae, Young Ho Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageGerman
Pages (from-to)1-6
Number of pages6
JournalZeitschrift fur Rheumatologie
DOIs
Publication statusAccepted/In press - 2018 Jul 5

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Random Allocation
Rheumatoid Arthritis
Alzheimer Disease
Mendelian Randomization Analysis
Genome-Wide Association Study
Meta-Analysis
Single Nucleotide Polymorphism
Genome

Keywords

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

ASJC Scopus subject areas

  • Rheumatology

Cite this

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title = "Kausalzusammenhang zwischen rheumatoider Arthritis und vermindertem Risiko f{\"u}r M. Alzheimer: Eine Mendel-Randomisierungsstudie",
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",
author = "Bae, {S. C.} and Lee, {Young Ho}",
year = "2018",
month = "7",
day = "5",
doi = "10.1007/s00393-018-0504-8",
language = "German",
pages = "1--6",
journal = "Zeitschrift fur Rheumatologie",
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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

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