Department of Spine, Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, Wuxi, Jiangsu, China.
PLoS One. 2024 Aug 27;19(8):e0305214. doi: 10.1371/journal.pone.0305214. eCollection 2024.
In a great many of observational studies, whether there is a relevance of resistin levels on bone mineral density (BMD) and fracture occurrence has been inconsistently reported, and the causality is unclear.
We aim to assess the resistin levels on BMD and fracture occurrence within a Mendelian randomization (MR) analysis. Exposure and outcome data were derived from the Integrative Epidemiology Unit (IEU) Open genome wide association studies (GWAS) database. Screening of instrumental variables (IVs) was performed subject to conditions of relevance, exclusivity, and independence. Inverse variance weighting (IVW) was our primary method for MR analysis based on harmonized data. Weighted median and MR-Egger were chosen to evaluate the robustness of the results of IVW. Simultaneously, heterogeneity and horizontal pleiotropy were also assessed and the direction of potential causality was detected by MR Steiger. Multivariable MR (MVMR) analysis was used to identify whether confounding factors affected the reliability of the results.
After Bonferroni correction, the results showed a suggestively positive causality between resistin levels and total body BMD (TB-BMD) in European populations over the age of 60 [β(95%CI): 0.093(0.021, 0.165), P = 0.011]. The weighted median [β(95%CI): 0.111(0.067, 0.213), P = 0.035] and MR-Egger [β(95%CI): 0.162(0.025, 0.2983), P = 0.040] results demonstrate the robustness of the IVW results. No presence of pleiotropy or heterogeneity was detected between them. MR Steiger supports the causal inference result and MVMR suggests its direct effect.
In European population older than 60 years, genetically predicted higher levels of resistin were associated with higher TB-BMD. A significant causality between resistin levels on BMD at different sites, fracture in certain parts of the body, and BMD in four different age groups between 0-60 years of age was not found in our study.
在大量观察性研究中，抵抗素水平与骨密度（BMD）和骨折发生之间的相关性存在不一致的报道，因果关系尚不清楚。
我们旨在通过孟德尔随机化（MR）分析评估抵抗素水平与 BMD 和骨折发生之间的关系。暴露和结局数据来自整合流行病学单位（IEU）开放全基因组关联研究（GWAS）数据库。根据相关性、排他性和独立性条件进行工具变量（IVs）筛选。基于协变量调整的 IVW 是我们进行 MR 分析的主要方法。加权中位数和 MR-Egger 用于评估 IVW 结果的稳健性。同时，还评估了异质性和水平多效性，并通过 MR Steiger 检测潜在因果关系的方向。多变量 MR（MVMR）分析用于确定是否存在混杂因素影响结果的可靠性。
经 Bonferroni 校正后，结果显示在年龄大于 60 岁的欧洲人群中，抵抗素水平与全身骨密度（TB-BMD）之间存在提示性正相关[β（95%CI）：0.093（0.021，0.165），P = 0.011]。加权中位数[β（95%CI）：0.111（0.067，0.213），P = 0.035]和 MR-Egger [β（95%CI）：0.162（0.025，0.2983），P = 0.040]结果表明 IVW 结果的稳健性。两者之间未检测到多效性或异质性。MR Steiger 支持因果推断结果，MVMR 表明其直接效应。
在年龄大于 60 岁的欧洲人群中，遗传预测的较高水平的抵抗素与较高的 TB-BMD 相关。本研究未发现不同部位 BMD、特定部位骨折与 0-60 岁四个不同年龄组之间的 BMD 之间存在显著的因果关系。
