Fleming Katy, Cornish Naomi, Vincent Emma E, Mumford Andrew D, Amulic Borko, Burley Kate
School of Cellular and Molecular Medicine, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, United Kingdom.
Translational Health Sciences, Bristol Medical School, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, United Kingdom.
J Leukoc Biol. 2025 Jul 9;117(7). doi: 10.1093/jleuko/qiaf076.
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.
中性粒细胞释放含有抗菌剂的细胞质颗粒是先天免疫的关键组成部分。中性粒细胞广泛参与组织炎症，然而，中性粒细胞对人类健康和疾病的贡献程度尚未完全明确。为了进一步探究这一点，我们利用公开可用的遗传数据，对中性粒细胞特征和14983种结局进行了孟德尔随机化全表型关联研究（MR-PheWAS）。中性粒细胞计数、颗粒度和血清髓过氧化物酶的遗传代理与145种结局相关。较高的中性粒细胞计数与较低的体重、降低的肥胖风险和增加的血管激活标志物相关，但与动脉粥样硬化无关。中性粒细胞计数升高与阿尔茨海默病密切相关，中性粒细胞颗粒度与肠道微生物群丰度和牙齿病理学相关。我们的研究结果揭示了中性粒细胞在病原体防御之外的多种作用，并强调了MR-PheWAS在识别新型中性粒细胞相关病理生理学方面的潜力。
