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. 2023 Sep 21;12(9):601-614.
doi: 10.1302/2046-3758.129.BJR-2023-0118.R1.

Appraising causal risk and protective factors for rheumatoid arthritis

Peng Gu  1 , Bin Pu  1 , Teng Liu  1 , Dan Yue  2 , Qiao Xin  3 , Hai-Shan Li  1 , Bai-Lin Yang  1 , Dao-Ze Ke  1 , Xiao-Hui Zheng  4 , Zhan-Peng Zeng  4 , Zhi-Qiang Zhang  5
Affiliations

Appraising causal risk and protective factors for rheumatoid arthritis

Peng Gu et al. Bone Joint Res. .

Abstract

Aims: Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies.

Methods: PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines.

Results: A total of 517 potentially relevant articles were screened, 35 studies were included in the systematic review, and 19 studies were eligible to be included in the meta-analysis. Pooled estimates of 19 included studies (causality between 15 different risk factors and RA) revealed that obesity, smoking, coffee intake, lower education attainment, and Graves' disease (GD) were related to the increased risk of RA. In contrast, the causality contribution from serum mineral levels (calcium, iron, copper, zinc, magnesium, selenium), alcohol intake, and chronic periodontitis to RA is not significant.

Conclusion: Obesity, smoking, education attainment, and GD have real causal effects on the occurrence and development of RA. These results may provide insights into the genetic susceptibility and potential biological pathways of RA.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Factors influencing rheumatoid arthritis (RA) in Mendelian randomization. Created with BioRender.com. TNF, tumour necrosis factor.
Fig. 2
Fig. 2
Preferred Reporting Items for Systematic review and Meta-Analyses flow diagram. MR, Mendelian randomization; RA, rheumatoid arthritis.
Fig. 3
Fig. 3
Meta-analysis results of the association between genetic liability to obesity-related indicators and risk of rheumatoid arthritis (RA). Estimates are odds ratios (ORs) with 95% confidence intervals (CIs) for a one-standard deviation increase in genetic liability to obesity-related indicators. a) Forest plot of causal relationship between BMI genetic susceptibility and RA risk. b) Forest plot of causal relationship between body fat percentage (BFP) genetic susceptibility and RA risk. c) Forest plot of causal relationship between favourable adiposity (FA) genetic susceptibility and RA risk. d) Forest plot of causal relationship between unfavourable adiposity (UFA) genetic susceptibility and RA risk. IV, inverse variance; SE, standard error.
Fig. 4
Fig. 4
Meta-analysis results of the association between genetic liability to phenotype of life environment and risk of rheumatoid arthritis (RA). Estimates are odds ratios (ORs) with 95% confidence intervals (CIs) for a one-standard deviation increase in genetic liability to phenotype of life environment. a) Forest plot of causal relationship between lifetime smoking genetic susceptibility and RA risk. b) Forest plot of causal relationship between alcoholic drinks genetic susceptibility and RA risk. c) Forest plot of causal relationship between coffee intake genetic susceptibility and RA risk. d) Forest plot of causal relationship between educational attainment genetic susceptibility and RA risk. IV, inverse variance; SE, standard error.
Fig. 5
Fig. 5
Meta-analysis results of the association between genetic liability to serum minerals and risk of rheumatoid arthritis (RA). Estimates are odds ratios (ORs) with 95% confidence intervals (CIs) for a one-standard deviation increase in genetic liability to serum minerals. a) Forest plot of causal relationship between serum Ca genetic susceptibility and RA risk. b) Forest plot of causal relationship between serum iron genetic susceptibility and RA risk. c) Forest plot of causal relationship between serum copper genetic susceptibility and RA risk. d) Forest plot of causal relationship between serum magnesium genetic susceptibility and RA risk. e) Forest plot of causal relationship between serum zinc genetic susceptibility and RA risk. f) Forest plot of causal relationship between serum selenium genetic susceptibility and RA risk. IV, inverse variance; SE, standard error.
Fig. 6
Fig. 6
Meta-analysis results of the association between genetic liability to disease status and risk of rheumatoid arthritis (RA). Estimates are odds ratios (ORs) with 95% confidence intervals (CIs). a) Forest plot of causal relationship between chronic periodontitis genetic susceptibility and RA risk. b) Forest plot of causal relationship between Graves' disease genetic susceptibility and RA risk. IV, inverse variance; SE, standard error.
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