Xiao Jiheng, Xia Tianyi, Zhou Xianglong, Xing Xin, Zhu Yanbin, Zhang Yingze, Xiong Liming
Department of Orthopaedics, Huazhong University of Science and Technology Tongji Medical College Union Hospital, Wuhan 430022, China.
Department of Orthopaedics, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.
Diagnostics (Basel). 2025 Jun 16;15(12):1526. doi: 10.3390/diagnostics15121526.
Intervertebral disc degeneration (IVDD) is caused by an imbalance between the catabolic and anabolic processes within intervertebral disc tissue. Several studies have suggested a potential association between cerebrospinal fluid metabolites (CFMs) and the development of IVDD. However, the existing evidence on the relationship between CFM and IVDD is limited and inconsistent. The data on 338 cerebrospinal fluid metabolites and intervertebral disc degeneration analyzed in this study were sourced from their respective genome-wide association studies (GWAS). MR analysis employed single nucleotide polymorphisms (SNPs) closely associated with disease as instrumental variables (IVs). The inverse variance weighted (IVW) method was employed as the primary statistical approach, complemented by MR-Egger, the Weighted median, Simple mode, and the Weighted mode for result validation. Comprehensive sensitivity analyses were performed to confirm the robustness of the results and assess for heterogeneity and horizontal pleiotropy. Using the IVW method, this study revealed positive causal effects between 11 cerebrospinal fluid metabolites (CFMs) and intervertebral disc degeneration (IVDD), indicating that elevated levels of these 11 CFMs increase the risk of IVDD. Conversely, negative causal effects were identified for 6 CFMs, suggesting that higher levels of these CFMs have a protective effect against IVDD. Reverse MR analysis indicated 1 positive and 18 negative causal relationships between IVDD and CFMs. Our bidirectional Mendelian analysis provides compelling evidence of a causal relationship between CFMs and IVDD. These findings enhance our understanding of IVDD pathogenesis and highlight the potential for preventive therapies targeting CFMs. Further research is needed to clarify the mechanisms of these CFMs on IVDD.
椎间盘退变（IVDD）是由椎间盘组织内分解代谢和合成代谢过程失衡引起的。多项研究表明脑脊液代谢物（CFMs）与IVDD的发生之间可能存在关联。然而，关于CFM与IVDD之间关系的现有证据有限且不一致。本研究分析的338种脑脊液代谢物和椎间盘退变的数据来自各自的全基因组关联研究（GWAS）。孟德尔随机化（MR）分析采用与疾病密切相关的单核苷酸多态性（SNPs）作为工具变量（IVs）。采用逆方差加权（IVW）方法作为主要统计方法，并辅以MR-Egger、加权中位数、简单模式和加权模式进行结果验证。进行了全面的敏感性分析，以确认结果的稳健性，并评估异质性和水平多效性。使用IVW方法，本研究揭示了11种脑脊液代谢物（CFMs）与椎间盘退变（IVDD）之间的正向因果效应，表明这11种CFMs水平升高会增加IVDD的风险。相反，确定了6种CFMs的负向因果效应，表明这些CFMs水平较高对IVDD有保护作用。反向MR分析表明IVDD与CFMs之间存在1个正向和18个负向因果关系。我们的双向孟德尔分析提供了CFMs与IVDD之间因果关系的有力证据。这些发现加深了我们对IVDD发病机制的理解，并突出了针对CFMs的预防性治疗的潜力。需要进一步研究以阐明这些CFMs对IVDD的作用机制。
