A comprehensive phenome wide analysis of the role of neutrophils in health and disease

Neutrophil release of cytoplasmic granules containing antimicrobial agents is a critical component of innate immunity. Neutrophils are widely implicated in tissue inflammation however the extent of the neutrophil contribution to human health and disease is incompletely characterized. To explore this further, we leveraged publicly available genetic data to conduct a Mendelian randomization phenome-wide association study (MR-PheWAS) of neutrophil traits and 14,983 outcomes. Genetic proxies for neutrophil count, granularity, and serum myeloperoxidase were linked to 145 outcomes. Higher neutrophil count was associated with lower body weight, reduced obesity risk, and increased vascular activation markers but not with atherosclerosis. Elevated neutrophil count was robustly linked to Alzheimer's disease and neutrophil granularity with gut microbiota abundance and dental pathology. Our findings reveal the diverse roles of neutrophils extending beyond pathogen defense and underscore the potential for MR-PheWAS in identifying novel neutrophil-related pathophysiology.