Investigating the causal effect of fibroblast growth factor 23 on osteoporosis and cardiometabolic disorders: A Mendelian randomization study
Investigating the causal effect of fibroblast growth factor 23 on osteoporosis and cardiometabolic disorders: A Mendelian randomization study
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DOI：
10.1016/j.bone.2020.115777
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发表时间：
2021-02-01
期刊：
影响因子：
4.1
通讯作者：
Ogawa, Yoshihiro
中科院分区：
文献类型：
--
作者：
Yokomoto-Umakoshi, Maki;Umakoshi, Hironobu;Ogawa, Yoshihiro
成纤维细胞生长因子 23 (FGF23) 病理性过量会导致矿物质和骨骼疾病。然而，FGF23 在骨质疏松症发展中的因果关系仍不清楚。除了调节矿物质代谢之外，FGF23 是否对心脏代谢紊乱具有系统性影响也存在争议。在这项研究中，我们使用孟德尔随机化 (MR) 分析研究了 FGF23 对骨质疏松症和心脏代谢紊乱的因果影响。从相关的全基因组关联研究中获得了具有感兴趣性状的单核苷酸多态性的汇总统计数据。结果发现，FGF23 与股骨颈 BMD（比值比 [OR] 0.682，95% 置信区间 [CI] 0.546-0.853，p = 8e-04）和跟部估计 BMD (eBMD)（OR 0.898，95% CI 0.820-0.985，p = 0.022）呈负相关。反方差加权分析，但不是腰椎 BMD 和骨折。结果得到加权中值分析的支持，并且 MR-Egger 分析中没有多效性的证据。在多变量 MR 分析中调整估计的肾小球滤过率、身高和体重指数后，FGF23 与 FN-BMD 和 eBMD 相关。另一方面，FGF23与心脏代谢特征之间没有关联，包括心脏病、臂踝脉搏波速度、颈动脉内膜中层厚度、收缩压和舒张压、空腹血糖、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇以及甘油三酯。因此，这项 MR 研究确定 FGF23 与骨质流失有关，相反，与心脏代谢紊乱无关。我们的研究结果为了解 FGF23 在骨质疏松症和心脏代谢疾病发病机制中的作用提供了重要见解。
Pathological excess of fibroblast growth factor 23 (FGF23) causes mineral and bone disorders. However, the causality of FGF23 in the development of osteoporosis remains unknown. Whether FGF23 has systemic effects on cardiometabolic disorders beyond regulating mineral metabolism is also controversial. In this study, we investigated the causal effect of FGF23 on osteoporosis and cardiometabolic disorders using Mendelian randomization (MR) analysis. Summary statistics for single-nucleotide polymorphisms with traits of interest were obtained from the relevant genome-wide association studies. As a result, FGF23 was found to be inversely associated with femoral neck-BMD (odds ratio [OR] 0.682, 95% confidence interval [CI] 0.546-0.853, p = 8e-04) and heel estimated BMD (eBMD) (OR 0.898, 95%CI 0.820-0.985, p = 0.022) in the inverse-variance-weighted analysis, but not lumbar spine-BMD and fractures. The results were supported by the weighted-median analysis, and there was no evidence of pleiotropy in the MR-Egger analysis. FGF23 was associated with FN-BMD and eBMD after adjustment for estimated glomerular filtration rate, height, and body mass index in multivariable MR analysis. On the other hand, there was no association between FGF23 and cardiometabolic traits including cardio artery disease, brachial-ankle pulse wave velocity, intima-media thickness of carotid arteries, systolic and diastolic blood pressure, fasting glucose, high and low-density lipoprotein cholesterol, and triglycerides. Therefore, this MR study established that FGF23 was involved in bone loss and, in contrast, was not involved in cardiometabolic disorders. Our findings provide important insights into the role of FGF23 in the pathogenesis of osteoporosis and cardiometabolic disorders.