Mendelian randomization analysis of the association between human blood cell traits and uterine polyps

Abstract

Human blood cells (HBCs) play essential roles in multiple biological processes but their roles in development of uterine polyps are unknown. Here we implemented a Mendelian randomization (MR) analysis to investigate the effects of 36 HBC traits on endometrial polyps (EPs) and cervical polyps (CPs). The random-effect inverse-variance weighted method was adopted as standard MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Genetic instruments of HBC traits was extracted from a large genome-wide association study of 173,480 individuals, while data for EPs and CPs were obtained from the UK Biobank. All samples were Europeans. Using genetic variants as instrumental variables, our study found that both eosinophil count (OR 0.85, 95% CI 0.79–0.93, P = 1.06 × 10−4) and eosinophil percentage of white cells (OR 0.84, 95% CI 0.77–0.91, P = 2.43 × 10−5) were associated with decreased risk of EPs. The results were robust in sensitivity analyses and no evidences of horizontal pleiotropy were observed. While we found no significant associations between HBC traits and CPs. Our findings suggested eosinophils might play important roles in the pathogenesis of EPs. Besides, out study provided novel insight into detecting uterine polyps biomarkers using genetic epidemiology approaches.

CoffeeProt: an online tool for correlation and functional enrichment of systems genetics data

“…CoffeeProt also identified rs2228467 as a trans- pQTL associated to eosinophil counts and Eotaxin (CCL11), a chemokine targeted by the monoclonal antibody Bertilimumab approved for the treatment of bullous pemphigoid in patients with eosinophilia. Importantly, both variants have recently been identified as causal for eosinophil counts using mendelian randomization (MR) analysis ( 43 ). While a recent phenome-wide MR study using >1000 plasma proteins included several bloody cell phenotypes ( 44 ), eosinophil counts were not included in the analysis and therefore further experiments are required to investigate potential causal roles of the identified proteins.…”

Epidermal Growth Factor Receptor Inhibition Prevents Caveolin-1-dependent Calcifying Extracellular Vesicle Biogenesis

“…MR uses genetic variants as IVs, where the unique genetic composition of each individual is used to "randomize" individuals into different treatment groups, mimicking a randomized control trial since genetic composition is randomized at birth [54]. The intuition in MR is that if genetic variants are correlated with the exposure variable and if the exposure variable is causal for the outcome variable, then the genetic variants should also explain variance in the outcome variable [55]. The IV assumptions must be fulfilled for MR to yield valid results, though in practice, they are often violated due to pleiotropic effects of genetic variants [30].…”