Mendelian Randomization Analysis Shows that Elevated Eosinophil Cell Count Increases the Risk of Autoimmune Disorders but Protects Against Skin Cancer

Abstract

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.