Department of Bone and Joint Surgery, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Medical Imaging Centre, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Front Immunol. 2024 Jul 18;15:1412298. doi: 10.3389/fimmu.2024.1412298. eCollection 2024.
Osteoporosis (OP) associated with aging exerts substantial clinical and fiscal strains on societal structures. An increasing number of research studies have suggested a bidirectional relationship between circulating inflammatory markers (CIMs) and OP. However, observational studies are susceptible to perturbations in confounding variables. In contrast, Mendelian randomization (MR) offers a robust methodological framework to circumvent such confounders, facilitating a more accurate assessment of causality. Our study aimed to evaluate the causal relationships between CIMs and OP, identifying new approaches and strategies for the prevention, diagnosis and treatment of OP.
We analyzed publicly available GWAS summary statistics to investigate the causal relationships between CIMs and OP. Causal estimates were calculated via a systematic analytical framework, including bidirectional MR analysis and Bayesian colocalization analysis.
Genetically determined levels of CXCL11 (OR = 0.91, 95% CI = 0.85-0.98, P = 0.008, P = 0.119), IL-18 (OR = 0.88, 95% CI = 0.83-0.94, P = 8.66×10-5, P = 0.008), and LIF (OR = 0.86, 95% CI = 0.76-0.96, P = 0.008, P = 0.119) were linked to a reduced risk of OP. Conversely, higher levels of ARTN (OR = 1.11, 95% CI = 1.02-1.20, P = 0.012, P = 0.119) and IFNG (OR = 1.16, 95% CI = 1.03-1.30, P = 0.013, P = 0.119) were associated with an increased risk of OP. Bayesian colocalization analysis revealed no evidence of shared causal variants.
Despite finding no overall association between CIMs and OP, five CIMs demonstrated a potentially significant association with OP. These findings could pave the way for future mechanistic studies aimed at discovering new treatments for this disease. Additionally, we are the first to suggest a unidirectional causal relationship between ARTN and OP. This novel insight introduces new avenues for research into diagnostic and therapeutic strategies for OP.
与衰老相关的骨质疏松症（OP）给社会结构带来了巨大的临床和财政压力。越来越多的研究表明，循环炎症标志物（CIMs）与 OP 之间存在双向关系。然而，观察性研究容易受到混杂变量的干扰。相比之下，孟德尔随机化（MR）提供了一种稳健的方法学框架，可以规避这些混杂因素，更准确地评估因果关系。我们的研究旨在评估 CIMs 与 OP 之间的因果关系，为 OP 的预防、诊断和治疗寻找新的方法和策略。
我们分析了公开的 GWAS 汇总统计数据，以研究 CIMs 与 OP 之间的因果关系。通过系统分析框架计算因果估计，包括双向 MR 分析和贝叶斯共定位分析。
遗传决定的 CXCL11 水平（OR=0.91，95%CI=0.85-0.98，P=0.008，P=0.119）、IL-18（OR=0.88，95%CI=0.83-0.94，P=8.66×10-5，P=0.008）和 LIF（OR=0.86，95%CI=0.76-0.96，P=0.008，P=0.119）与 OP 风险降低相关。相反，较高的 ARTN（OR=1.11，95%CI=1.02-1.20，P=0.012，P=0.119）和 IFNG（OR=1.16，95%CI=1.03-1.30，P=0.013，P=0.119）水平与 OP 风险增加相关。贝叶斯共定位分析未发现共享因果变异的证据。
尽管我们没有发现 CIMs 与 OP 之间存在总体关联，但有五种 CIMs 与 OP 存在潜在的显著关联。这些发现可能为未来针对这种疾病的治疗机制研究铺平道路。此外，我们是第一个提出 ARTN 与 OP 之间存在单向因果关系的人。这一新的见解为 OP 的诊断和治疗策略研究开辟了新的途径。
