No causal association between pneumoconiosis and three inflammatory immune diseases: a Mendelian randomization study

Our plain-English summary of No causal association between pneumoconiosis and three inflammatory immune diseases: a Mendelian randomization study, by Y.J. Du, Z.W. Lu, K.D. Li, et al (Frontiers in Public Health, 2024).

The study

• Authors: Y.J. Du, Z.W. Lu, K.D. Li, Y.Y. Wang, H. Wu, R.G. Huang, X. Jin, Y.Y. Wang, J. Wang, A.Y. Geng, B.Z. Li
• Journal: Frontiers in Public Health
• Published: 2024;12:1373044
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: To investigate the causal relationships between pneumoconiosis and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and gout.

Methods: The random-effects inverse variance weighted (IVW) approach was utilized to explore the causal effects of the instrumental variables (IVs). Sensitivity analyses using the MR-Egger and weighted median (WM) methods were did to investigate horizontal pleiotropy. A leave-one-out analysis was used to avoid the bias resulting from single-nucleotide polymorphisms (SNPs).

Results: There was no causal association between pneumoconiosis and SLE, RA or gout in the European population [OR = 1.01, 95% CI: 0.94-1.10, p = 0.74; OR = 1.00, 95% CI: 0.999-1.000, p = 0.50; OR = 1.00, 95% CI: 1.000-1.001, p = 0.55]. Causal relationships were also not found in pneumoconiosis due to asbestos and other mineral fibers and SLE, RA and gout [OR = 1.01, 95% CI: 0.96-1.07, p = 0.66; OR = 1.00, 95% CI: 1.00-1.00, p = 0.68; OR = 1.00, 95% CI: 1.00-1.00, p = 0.20].

Conclusion: Our study suggests that pneumoconiosis may have no causal relationship with the three inflammatory immune diseases.

Copyright © 2024 Du, Lu, Li, Wang, Wu, Huang, Jin, Wang, Wang, Geng and Li.

In plain English

This was a Mendelian randomization study. The method uses genetic variants as stand-ins to test whether one condition causes another. The authors used published summary-level genetic data from people of European origin. They tested whether pneumoconiosis in general, and separately 'pneumoconiosis due to asbestos and other mineral fibers' (235 cases, 216,866 controls), causes rheumatoid arthritis, systemic lupus erythematosus or gout. In the main analysis, neither form showed a statistically significant link with any of the three diseases. For lupus, odds ratios were 1.01 (95% confidence interval 0.94 to 1.10) for pneumoconiosis and 1.01 (0.96 to 1.07) for the asbestos-related form. For rheumatoid arthritis they were 1.00 (0.999 to 1.000) and 1.00 (1.00 to 1.00). For gout they were 1.00 (1.000 to 1.001) and 1.00 (1.00 to 1.00). All of these were printed rounded. The authors found no sign that the variants worked through other pathways. Results for general pneumoconiosis and gout varied across variants. The authors concluded that pneumoconiosis may have no causal relationship with these diseases. They noted possible false positives from relaxed variant selection, a European-only population, and no separate analysis of other causes.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Two-sample Mendelian randomization study using published genome-wide association (GWAS) summary data.
• Who was studied: Summary genetic data from people of European origin, from the European Bioinformatics Institute GWAS Catalogue and the FinnGen consortium. According to Table 1, pneumoconiosis had 433 cases and 478,607 controls. Pneumoconiosis due to asbestos and other mineral fibers had 235 cases and 216,866 controls. Lupus had 647 cases, rheumatoid arthritis 5,427 cases and gout 6,810 cases.
• Exposure: Genetic variants associated with diagnosed pneumoconiosis, and separately with pneumoconiosis due to asbestos and other mineral fibers (FinnGen). No fiber types, jobs or doses were measured.
• Main results:
  • Pneumoconiosis (general) and lupus, main (IVW) analysis: OR 1.01, 95% CI 0.94 to 1.10, p = 0.74. This was not statistically significant.
  • Pneumoconiosis (general), main (IVW) analysis, not statistically significant. Rheumatoid arthritis: OR 1.00, 95% CI 0.999 to 1.000, p = 0.50. Gout: OR 1.00, 95% CI 1.000 to 1.001, p = 0.55.
  • Pneumoconiosis due to asbestos and other mineral fibers, not statistically significant. Lupus: OR 1.01, 95% CI 0.96 to 1.07, p = 0.66. Rheumatoid arthritis: OR 1.00, 95% CI 1.00 to 1.00, p = 0.68.
  • Pneumoconiosis due to asbestos and other mineral fibers and gout: OR 1.00, 95% CI 1.00 to 1.00, p = 0.20. No causal relationship was found.
  • For gout, results for general pneumoconiosis showed heterogeneity across variants (p = 0.01). Results for the asbestos-related form did not (p = 0.47).
  • No horizontal pleiotropy was detected in the lupus analyses (p = 0.23; p = 0.88). The authors therefore considered those results credible.
• The authors' conclusion: The authors concluded that pneumoconiosis may have no causal relationship with rheumatoid arthritis, lupus or gout. They added that further research is needed to validate this and clarify the mechanism.
• Limitations the authors state:
  • The variant selection criterion was relaxed because few variants met the usual requirements, which might produce false positives.
  • Only European populations were studied, so it is unknown whether other populations show the same pattern.
  • No GWAS data were available for pneumoconiosis caused by other exposures, so the different causes of pneumoconiosis could not be analyzed separately.
  • The database had no information on blood markers of systemic inflammation.

Topics

Medical terms in this study, explained in our Lexicon: Pneumoconiosis, Mineral Fiber.

Related studies

• Tracheal carcinoma and mixed pneumoconiosis. A causal relationship? — D. Theegarten, S. Philippou, et al. (1995)
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• WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of occupational exposure to dusts and/or fibres and of the effect of occupational exposure to dusts and/or fibres on pneumoconiosis — D. Mandrioli, V. Schlünssen, et al. (2018)
• Relationship of inflammatory cell cytokines to disease severity in individuals with occupational inorganic dust exposure — W.N. Rom (1991)
• Carborundum pneumoconiosis. Fibers in the mineral activate macrophages to produce fibroblast growth factors and sustain the chronic inflammatory disease — R. Bégin, A. Dufresne, et al. (1989)
• Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development — T.A. Brown, A. Holian, et al. (2016)

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