Tumor necrosis factor mediates the impact of PM2.5 on bone mineral density: Inflammatory proteome Mendelian randomization and colocalization analyses

Autor: Mingzheng Li, Peng Shi, Huajie Yang, Suyuan Tong, Nianfeng Qiu, Fan Yao, Yuan Du, Shuhua Xi, Fei Wang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Ecotoxicology and Environmental Safety, Vol 270, Iss , Pp 115896- (2024)
Druh dokumentu: article
ISSN: 0147-6513
DOI: 10.1016/j.ecoenv.2023.115896
Popis: To assess the causal effect of particulate matter 2.5 (PM2.5) on human bone mineral density (BMD) and to explore the possible mechanism and proportion mediated by inflammation-related protein. The genetic correlation between PM2.5 and BMD was assessed using the Linkage Disequilibrium Score (LDSC), and the causal effect between PM2.5 and BMD was assessed by two-sample Mendelian randomization (TSMR). A 2-step Mendelian randomization (MR) approach was employed to evaluate the potential role of inflammation-associated protein as the mediator in the causal association between PM2.5 and BMD. The multivariate Mendelian randomization (MVMR) study was designed to perform mediation analyses, exclude possible confounders and calculate the proportion of mediation. Subsequently, we used Bayesian colocalization analysis to consolidate the MR results. Finally, using drug-target MR design, we evaluated the potential repurposing of tumor necrosis factor (TNF) inhibitors for the treatment of osteoporosis (OP). The results of the analyses show that BMD is negatively influenced by PM2.5 (Inverse variance weighted [IVW] beta [β] = −0.288, 95% confidence interval [CI]: −0.534 – −0.042, P 0.05). After adjusting PM2.5 and TAC-1, there was still a negative causal association between TNF and BMD (IVW β = −0.089, 95% CI: −0.166 – −0.012, P
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