Asthma and atopic dermatitis as risk factors for rheumatoid arthritis: a bidirectional mendelian randomization study

Chen, Chuiji; Su, Le; Duan, Wenhao; Zheng, Yan; Zhang, Dianzhong; Wang, Yucai

doi:10.1186/s12920-023-01461-7

Cited by 9 publications

(8 citation statements)

References 54 publications

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“…To our knowledge, there have been four MR studies based on European populations assessing the potential causal relationship between RA and asthma or COPD [16][17][18][19] The conclusions from Cao et al [19] are similar to ours, showing a positive association between genetically predicted RA and risk of COPD or asthma, however, they didn't conduct reverse MR studies. The conclusions from Yu et al…”

Section: Discussionsupporting

confidence: 68%

“…This approach leverages the stochastic allocation of genetic variations at conception [15]. To date, MR studies conducted in European populations have yielded various conclusions [16][17][18][19]. Chen [17] utilized summary statistics for asthma (56,167 cases and 352,255 controls) and RA (2,843 cases and 5,540 controls) from IEU Open GWAS, employing 53 asthma-related SNPs and 40 RA-related SNPs as IVs.…”

Section: Introductionmentioning

confidence: 99%

“…To date, MR studies conducted in European populations have yielded various conclusions [16][17][18][19]. Chen [17] utilized summary statistics for asthma (56,167 cases and 352,255 controls) and RA (2,843 cases and 5,540 controls) from IEU Open GWAS, employing 53 asthma-related SNPs and 40 RA-related SNPs as IVs. The ndings indicated a causal relationship between genetic susceptibility to asthma and an increased risk of RA, yet found no evidence to support a causal relationship between RA genetic susceptibility and asthma.…”

Section: Introductionmentioning

confidence: 99%

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Association Between Rheumatoid Arthritis and Chronic Respiratory Diseases in A Japanese Population: A Mendelian Randomization Study

Shen,

Zeng,

Wei

et al. 2024

Preprint

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Objective Past observational studies have documented an association between Rheumatoid Arthritis (RA) and Chronic Respiratory Diseases (CRD). However, the establishment of a causal link remains elusive. Undertaking the approach of Mendelian Randomization (MR) analysis, this research aims to delve deeper into the probability of a causal connection between RA and CRD within the Japanese population. Methods Collated genome-wide association study (GWAS) data covering RA with 4,199 cases against 208,254 controls, asthma comprising 8,216 cases versus 201,592 controls, and Chronic Obstructive Pulmonary Disease (COPD) detailing 3,315 cases in contrast to 201,592 controls were derived from the repository of the Japanese Biobank. A selection of ten RA-related, eight asthma-related, and four COPD-related single nucleotide polymorphisms (SNPs) notable for their statistical significance (P < 5×10^−8) were identified as instrumental variables. The primary analytical technique employed to compute the odds ratios (ORs) and 95% confidence intervals (95%CIs) was the inverse variance-weighted (IVW) method, alongside the MR-Egger's protocol, weighted median, and weighted mode to reinforce the validity and solidity of the principal results. For scrutinizing possible implications of horizontal pleiotropy, we harnessed the MR-Egger’s intercept examination and the Mendelian Randomization Pleiotropy REsidual Sum and Outlier (MRPRESSO) test. Results Employing the inverse variance-weighted technique, we established a positive correlation between genetic predispositions for RA and actual occurrences of asthma (OR = 1.14; 95% CI: 1.04–1.24; P = 0.003). This correlation remained strong when testing the results utilizing various methods, including the MR-Egger's method (OR = 1.32; 95% CI: 1.09–1.60; P = 0.023), the weighted median (OR = 1.16; 95% CI: 1.06–1.26; P < 0.001), and the weighted mode (OR = 1.21; 95% CI: 1.11–1.32; P = 0.002). Furthermore, our findings from the inverse variance-weighted method also demonstrated a positive association between genetically predicted RA and COPD (OR = 1.12; 95% CI: 1.02–1.29; P = 0.021). However, no such link was discerned in supplementary analyses. In a shifted perspective - the reverse MR analysis - no correlation was identified between genetically predicted instances of asthma (IVW, P=0.717) or COPD (IVW, P=0.177) and RA. Conclusion Our study's findings confirm a causal correlation between genetically predicted RA and an elevated risk of either asthma or COPD. In contrast, our results offer no support to the presumed causal relationship between genetic susceptibility to either asthma or COPD and the subsequent development of RA. We underscore the necessity of additional MR studies, particularly when future GWAS present more comprehensive data for RA, asthma, and COPD within distinct East Asian or Japanese populations.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association Between Rheumatoid Arthritis and Chronic Respiratory Diseases in A Japanese Population: A Mendelian Randomization Study

Shen,

Zeng,

Wei

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…The effect sizes were represented by the odds ratio (OR) and standard error (SE). We used the IVW method and MR-Egger regression to evaluate the presence of heterogeneity in the results, as assessed by Cochran's Q-test (24).…”

Section: Mendelian Randomization Analysesmentioning

confidence: 99%

Non-alcoholic Fatty Liver Disease as risk factors for Chronic Kidney Disease: A Bidirectional Mendelian Randomization Study

Chen,

Nian,

Zheng

2023

Preprint

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Background Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) are two significant global public health concerns. Recent reports suggest that NAFLD may increase the risk of developing CKD. However, the specific causal relationship between these two conditions has not been thoroughly investigated. Methods In this study, we analyzed genome-wide association study (GWAS) summary data of CKD and NAFLD. We identified single nucleotide polymorphisms (SNPs) associated with these diseases as instrumental variables (IVs) at a genome-wide significance level (P < 1.0 × 10− 5) at first. Then, for Mendelian randomization (MR) analysis, we primarily used the inverse variance weighted (IVW) method, while employing the MR-Egger, weighted model, simple model, and weighted median methods for quality control. We also conducted sensitivity analysis to ensure the robustness of the results. Results Our MR analysis revealed a significant association between genetically predicted NAFLD and an increased risk of CKD using the IVW method (OR, 0.94; 95% CI, 0.89–1.00; P = 0.049). However, we found no evidence to support a causal relationship between CKD on NAFLD (IVW: P = 0.467). Conclusion Based on our findings, there is a causal relationship between NAFLD and CKD. Further investigations are necessary to elucidate the impact of these two diseases, as our results do not support a causal effect of CKD on NAFLD.

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“…Next, the MR-Egger intercept allows for the assessment of horizontal pleiotropy, with a p-value > 0.05 indicating no substantial evidence of such pleiotropic effects [24]. Furthermore, a leave-one-out sensitivity analysis was conducted to identify and exclude individual IVs that exerted a signi cant independent in uence on the MR results [25]. 3.…”

Section: Sensitivity Analysesmentioning

confidence: 99%

Causal relationship between rheumatoid arthritis and thyroid dysfunction: A two-sample Mendelian randomization study

Sun

Dong-chu²,

Xiao³

et al. 2023

Preprint

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Background Growing evidence has shown that Rheumatoid arthritis (RA) is associated with hyperthyroidism and hypothyroidism.However, the reciprocal cause-and-effect relationship among those three factors has not yet been substantiated. Methods We conducted a two-sample Mendelian randomization (TSMR) study with bidirectional analysis. We selected specific single nucleotide polymorphisms (SNPs) associated with rheumatoid arthritis (RA), hyperthyroidism, and hypothyroidism as instrumental variables. Every single nucleotide polymorphism (SNP) was derived from a genome-wide association study conducted specifically on individuals of European ancestry. For this study, the primary approach utilized to estimate the reciprocal causal relationship between rheumatoid arthritis (RA) and hyperthyroidism or hypothyroidism was the inverse-variance weighting (IVW) method. Finally, the robustness of the results was tested using sensitivity analysis and pleiotropic test. Results The utilization of the IVW method to detect rheumatoid arthritis (RA) revealed an elevated relative risk of hyperthyroidism (OR=1.33, 95% CI=1.17-1.52, P=2.407e-05), as well as a heightened risk of hypothyroidism (OR=1.29, 95% CI: 1.21-1.37, P=3.614e-16). On the flip side, it was observed that hypothyroidism might also elevate the relative risk of developing rheumatoid arthritis (OR=1.57, 95% CI=1.30-1.91, P=4.211e-06). Nevertheless, the analysis using the inverse-variance weighting (IVW) method suggested that there might not be a causal relationship between hyperthyroidism and rheumatoid arthritis (IVW: P=0.769). Finally, a sensitivity analysis was performed to assess the reliability of the results, and it indicated that no pleiotropic effects were observed, further bolstering the validity of the findings. Conclusion The findings of this study demonstrate a bidirectional causal relationship between genetic susceptibility to rheumatoid arthritis (RA) and an augmented risk of developing hypothyroidism, and vice versa. Moreover, this research establishes a positive causal relationship between genetic susceptibility to rheumatoid arthritis (RA) and an elevated risk of hyperthyroidism. However, it does not provide evidence to support a causal relationship between genetic susceptibility to hyperthyroidism and the development of RA.

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Asthma and atopic dermatitis as risk factors for rheumatoid arthritis: a bidirectional mendelian randomization study

Cited by 9 publications

References 54 publications

Association Between Rheumatoid Arthritis and Chronic Respiratory Diseases in A Japanese Population: A Mendelian Randomization Study

Association Between Rheumatoid Arthritis and Chronic Respiratory Diseases in A Japanese Population: A Mendelian Randomization Study

Non-alcoholic Fatty Liver Disease as risk factors for Chronic Kidney Disease: A Bidirectional Mendelian Randomization Study

Causal relationship between rheumatoid arthritis and thyroid dysfunction: A two-sample Mendelian randomization study

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