White blood cells and chronic rhinosinusitis: a Mendelian randomization study

Abstract

Background Risk factors for the pathogenesis of chronic rhinosinusitis (CRS) remain largely undetermined, which is likely due to the heterogeneity of the disease. White blood cell counts have been largely unexplored as a risk factor for CRS even though different types of white blood cells are involved in the inflammatory process of CRS. Objective To investigate causal associations between different types of white blood cells on risk of CRS utilizing a Mendelian randomization (MR) analysis. Methods A two-sample MR analysis was performed using respective GWAS summary statistics for the exposure traits (neutrophil count, eosinophil count, basophil count, lymphocyte count, and monocyte count) and outcome trait (CRS). For the exposure traits, the European Bioinformatics Institute database of complete GWAS summary data was used. For the outcome trait, summary statistics for CRS GWAS were obtained from FinnGen. Primary analysis for MR was performed using inverse-variance weighted two-sample MR. Sensitivity analyses included weighted median, MR-Egger, and MR-PRESSO (raw and outlier-corrected). Results Eosinophils were associated with CRS (OR = 1.55 [95% CI 1.38, 1.73]; p = 4.3E-14). Eosinophil results were similar across additional MR methods. MR results did not demonstrate significant causal relationships between neutrophils, lymphocytes, monocytes, or basophils with CRS. No significant pleiotropic bias was observed. Conclusions In a two-sample MR analysis, a potential causal link between blood eosinophil counts and CRS has been demonstrated. In addition, causal relationships between blood counts among other white blood cell types and CRS were not found. Further studies involving genetic variation in CRS are needed to corroborate genetic causal effects for CRS.

Gastroesophageal Reflux Disease and Rhinosinusitis: A Bidirectional Mendelian Randomization Study

“…It deserves further investigation into which phenotypes or endotypes of CRS are more likely to be caused by GERD. Some MR studies showed that peripheral eosinophils were significantly associated with GERD, whereas there was no evidence to link neutrophils, monocytes, and lymphocytes with GERD [34]. In addition, it is unclear whether inflammatory cell counts in peripheral blood help assess the association between GERD and nasal inflammation.…”

Association between multiple sclerosis and cancer risk: A two-sample Mendelian randomization study

“…Phenoscanner database ( http://www.phenoscanner.medschl.cam.ac.uk/ ) was used to identify associations with confounders and outcomes. We calculated F -statistic to evaluate the strength of the instruments and F -statistic > 10 indicated sufficient strength [ 29 ]. The calculation is: F = 2 × MAF × (1− MAF ) β 2 ( N −2) / [1−2 × MAF × (1− MAF ) β 2 ], MAF is the minor allele frequency, β is the estimated corresponding effect and N is the exposure GWAS sample size.…”

“…Phenoscanner database (http://www.phenoscanner.medschl.cam.ac.uk/) was used to identify associations with confounders and outcomes. We calculated F-statistic to evaluate the strength of the instruments and F-statistic > 10 indicated sufficient strength [29].…”

Integrative Mendelian Randomization approaches for therapeutic target prioritisation in immune-mediated diseases

“…Here, we propose a new intermediate trait category for use in proxying drug targets in IMD: immune cell abundance. There is substantial animal model, observational and MR evidence [21][22][23][24][25][26] implicating immune cell dysregulation in the pathogenesis of immune-mediated disorders, ranging from roles of T H 2 cells, eosinophils, and neutrophils in allergic conditions like asthma [27,28] and eczema [29,30] to expansion of certain T helper lymphocyte and B lymphocyte lineages in autoimmune diseases such as systemic lupus erythematosus (SLE) [31], multiple sclerosis [32] and rheumatoid arthritis [5]. Furthermore, approved drug targets for IMD are usually classed as immunosuppressants or immunomodulators, which alter the balance of immune blood cells in their course of on-target action.…”