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| 脑-骨轴下脑皮质与脑脊液代谢物对骨关节炎的遗传研究 |
| Genetic study of metabolites in cerebral cortex and cerebrospinal fluid under brain bone axis on osteoarthritis |
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| DOI：10.3969/j.issn.1006-7108.2026.06.006 |
| 中文关键词: 骨关节炎 脑-骨轴 孟德尔随机化 脑脊液代谢物 大脑皮质结构 |
| 英文关键词:osteoarthritis brain-bone axis mendelian randomization cerebrospinal fluid metabolites cortical structure |
| 基金项目:江苏省中医药领军人才培养项目（SLJ0310）；江苏省重点学科和医学重点实验室（苏卫科教[2022]17号）；苏州市中医骨科重点实验室（苏财教[2022]141号）；江苏省中医药科技发展项目(MS2022080) |
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| 中文摘要: |
| 目的 探讨脑脊液代谢物、大脑皮质结构与骨关节炎及其两种亚型的相关性。方法 基于全基因组关联研究的汇总数据，我们将338个脑脊液代谢物及70个大脑皮质结构与骨关节炎及其两个主要亚型髋关节炎、膝关节炎分别进行双向两样本孟德尔分析。以逆方差加权法为主，结合MR-Egger 回归法、加权中位数法，分析可能的因果关系，并通过敏感性分析增加结果稳健性。另外，通过多变量孟德尔随机化校正多个暴露因素对同一结局的影响，并采用中介MR传统两步法验证可能的介导关系。结果 共得到55种可能的因果关联，其中古洛糖酸水平对骨关节炎，异戊酸、1-棕榈酰-2-硬脂酰-GPC（16:0/18:0），1-油酰基-GPC（18:1）对膝关节炎有较显著的影响，经多变量分析MR后提示异戊酸仍与膝关节存在因果关联。通过筛选阳性交集，得到5种可能的中介介导关系。结论 脑脊液代谢物及大脑皮质通过代谢紊乱、神经系统调节、炎症反应等方式在骨关节炎及其两种亚型病理进程中产生重要作用，大脑皮质在脑脊液代谢物影响骨关节炎及其两种亚型中可能存在中介作用。 |
| 英文摘要: |
| Objective To explore the association between cerebrospinal fluid metabolites, cerebral cortex structures, and osteoarthritis. Methods Using summary-level GWAS data, we conducted bidirectional two-sample Mendelian randomization analyses on 338 cerebrospinal fluid metabolites and 70 cortical structures for osteoarthritis and its two main subtypes: hip osteoarthritis and knee osteoarthritis. The inverse variance-weighted (IVW) method was the primary approach, supplemented by MR-Egger and weighted median methods, to explore potential causal relationships. Sensitivity analyses were performed to enhance the robustness of the results. Additionally, multivariable MR was used to adjust for the effects of multiple exposures on the same outcome. Mediation analyses were conducted using the traditional two-step MR method to validate potential mediating relationships. Results A total of 55 potential causal associations were identified. Among these, Gulonate levels showed significant effects on osteoarthritis, while Isovalerate (i5:0), 1-palmitoyl-2-stearoyl-gpc (16:0/18:0), and 1-oleoyl-GPC (18:1) were significantly associated with knee osteoarthritis. Multivariable MR analysis indicated that Isovalerate (i5:0) maintained a causal association with knee osteoarthritis. Screening for positive intersections identified five potential mediating relationships. Conclusion Cerebrospinal fluid metabolites and cerebral cortex play an important role in the pathological process of osteoarthritis and its two subtypes through metabolic disorders, nervous system regulation, inflammatory reactions and other ways. Cerebral cortex may play an intermediary role in the influence of cerebrospinal fluid metabolites on osteoarthritis and its two subtypes. |
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