Peng Run, Wang Xiaoxin, Wang Wei, Li Zeqin, Sun Yuze, Yang Mingliang
School of Rehabilitation Medicine, Capital Medical University, Beijing, China.
Department of Spinal and Neural Functional Reconstruction, China Rehabilitation, Research Center, Beijing, China.
Hereditas. 2025 Feb 7;162(1):18. doi: 10.1186/s41065-025-00374-y.
Observational studies have shown an association between cerebrospinal fluid (CSF) metabolites and low back pain (LBP), but the causal relationship between these factors remains unclear.
We performed a two-sample Mendelian randomization (MR) analysis to examine whether there is a causal relationship between CSF metabolites and LBP. We applied several MR methods, including inverse variance weighting, weighted median, MR-Egger, Wald ratio, and MR-PRESSO, to test the causal relationship and conducted a sensitivity analysis to assess the robustness of the results.
We identified a total of 12 CSF metabolites significantly associated with LBP, of which Bilirubin, 5,6-dihydrothymine, Erythronate, Mannitol/sorbitol, and Butyrate have a potential inhibitory causal effect on LBP risk (p < 0.05). Meanwhile, 2-hydroxyadipate, Gamma-glutamyl-alpha-lysine, Indoleacetate, N-acetylputrescine, Palmitoyl dihydrosphingomyelin, S-methylcysteine, and 2,3-dihydroxy-5-methylthio-4-pentenoate play a causal role in increasing the risk of LBP (p < 0.05). No significant estimates of heterogeneity or pleiotropy were detected.
Our study emphasizes the causal relationship between CSF metabolites and LBP risk, providing reference for clinical treatment and prognosis of LBP.
观察性研究表明脑脊液（CSF）代谢物与腰痛（LBP）之间存在关联，但这些因素之间的因果关系仍不清楚。
我们进行了两样本孟德尔随机化（MR）分析，以检验CSF代谢物与LBP之间是否存在因果关系。我们应用了几种MR方法，包括逆方差加权、加权中位数、MR-Egger、Wald比率和MR-PRESSO，来检验因果关系，并进行了敏感性分析以评估结果的稳健性。
我们共鉴定出12种与LBP显著相关的CSF代谢物，其中胆红素、5,6-二氢胸腺嘧啶、赤藓糖酸盐、甘露醇/山梨醇和丁酸盐对LBP风险具有潜在的抑制因果效应（p < 0.05）。同时，2-羟基己二酸、γ-谷氨酰-α-赖氨酸、吲哚乙酸、N-乙酰腐胺、棕榈酰二氢鞘氨醇、S-甲基半胱氨酸和2,3-二羟基-5-甲硫基-4-戊烯酸在增加LBP风险方面起因果作用（p < 0.05）。未检测到显著的异质性或多效性估计。
我们的研究强调了CSF代谢物与LBP风险之间的因果关系，为LBP的临床治疗和预后提供了参考。
