Mendelian Randomization Analysis Shows that Elevated Eosinophil Cell Count Increases the Risk of Autoimmune Disorders but Protects Against Skin Cancer
DOI:
https://doi.org/10.47611/jsrhs.v11i3.3026Keywords:
Mendelian Randomization, oncology, cancer, blood cells, skin cancer, R programming, autoimmune diseases, eosinophil cellsAbstract
Background: Eosinophils are immune cells which are critical to the pathophysiology of autoimmune disorders and skin cancer. We performed an integrated causal inference analysis with Mendelian randomization to demonstrate that although individuals with reduced eosinophil cell count are protected against autoimmune disorders such as asthma, they are at increased risk of skin cancer.
Methods: Epidemiology and public health has historically relied on observational studies to identify risk factors for disease; however, these methods are limited by reverse causation and confounding effects. In this study, we utilize genetic epidemiology and Mendelian randomization, a methodology that removes the risk for reverse causation, reduces pathways for confounding variables, and is an effective tool in identifying causal effects between risk factors and outcomes. Our analysis combines results from 12 genetic analyses from 5 different studies to explore the differential effect of eosinophil cell count on autoimmune and skin cancer disease risk.
Results: Raised eosinophil count resulted in increased risk of multiple autoimmune disorders including psoriasis (OR 0.0029 (95% CI: 0.0013-0.0046), P-value = 5.0x10-4), ankylosing spondylitis (OR 1.397x10-3 (95% CI: 0.0006-0.002), P-value = 4.0x10-4), and rheumatoid arthritis (OR 0.0011 (95% CI: 0.0004-0.0019), P-value = 2.1x10-3). In contrast, increased eosinophil cell count was protective against malignant melanoma (OR -0.001 (95% CI: -0.0017-(-0.0003)), P-value = 0.0074) and basal cell carcinoma (OR -0.0012 (95% CI: -0.0024-(-0.00007)), P-value = 3.7x10-2).
Conclusions: Results indicated that the causal effect of increased eosinophil count differentially increases the risk of immune related disorders and decreases the risk of oncology related skin diseases.
Downloads
References or Bibliography
Biton, J., Khaleghparast Athari, S., Thiolat, A., Santinon, F., Lemeiter, D., Hervé, R., Delavallée, L., Levescot, A., Roga, S., Decker, P., Girard, J.-P., Herbelin, A., Boissier, M.-C., & Bessis, N. (2016). In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis. Journal of Immunology , 197(5), 1708–1719. https://doi.org/10.4049/jimmunol.1502124
Lin, Z., Deng, Y., & Pan, W. (2021). Combining the strengths of inverse-variance weighting and Egger regression in Mendelian randomization using a mixture of regressions model. PLoS Genetics, 17(11), e1009922. https://doi.org/10.1371/journal.pgen.1009922
Moreira, A., Leisgang, W., Schuler, G., & Heinzerling, L. (2017). Eosinophilic count as a biomarker for prognosis of melanoma patients and its importance in the response to immunotherapy. Immunotherapy, 9(2), 115–121. https://doi.org/10.2217/imt-2016-0138
Qin, Y., Jin, H.-Z., Li, Y.-J., & Chen, Z. (2021). Emerging Role of Eosinophils in Resolution of Arthritis. Frontiers in Immunology, 12, 764825. https://doi.org/10.3389/fimmu.2021.764825
Travers, J., & Rothenberg, M. E. (2015). Eosinophils in mucosal immune responses. Mucosal Immunology, 8(3), 464–475. https://doi.org/10.1038/mi.2015.2
Varricchi, G., Galdiero, M. R., Loffredo, S., Lucarini, V., Marone, G., Mattei, F., Marone, G., & Schiavoni, G. (2018). Eosinophils: The unsung heroes in cancer? Oncoimmunology, 7(2), e1393134. https://doi.org/10.1080/2162402X.2017.1393134
Published
How to Cite
Issue
Section
Copyright (c) 2022 Aryamann Singh; Parsa Akbari
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Copyright holder(s) granted JSR a perpetual, non-exclusive license to distriute & display this article.