中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (30): 6574-6582.doi: 10.12307/2025.911

• 组织构建相关数据分析 Date analysis of organization construction • 上一篇    下一篇

神经影像学变化与骨坏死的关联:UK Biobank及FinnGen数据库的大样本分析

张博淳1,李  威1,李广政1,丁浩秦1,李  刚2,梁学振1,2   

  1. 1山东中医药大学第一临床医学院,山东省济南市  250355;2山东中医药大学附属医院显微骨科,山东省济南市  250014

  • 收稿日期:2024-10-18 接受日期:2024-11-26 出版日期:2025-10-28 发布日期:2025-03-29
  • 通讯作者: 梁学振,博士,副教授,硕士生导师,山东中医药大学第一临床医学院,山东省济南市 250355;山东中医药大学附属医院显微骨科,山东省济南市 250014
  • 作者简介:张博淳,男,2000年生,辽宁省朝阳市人,汉族,硕士,主要从事中医骨伤科学方面的研究。
  • 基金资助:
    国家自然科学基金面上项目(82074453),项目负责人:李刚;国家自然科学基金青年项目(82205154),项目负责人:梁学振;山东省自然科学基金青年项目(ZR2021QH004),项目负责人:梁学振;山东省自然科学基金面上项目(ZR2024MH156),项目负责人:梁学振

Association between neuroimaging changes and osteonecrosis: a large sample analysis from UK Biobank and FinnGen databases

Zhang Bochun1, Li Wei1, Li Guangzheng1, Ding Haoqin1, Li Gang2, Liang Xuezhen1, 2   

  1. 1First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China; 2Department of Orthopaedic Microsurgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China
  • Received:2024-10-18 Accepted:2024-11-26 Online:2025-10-28 Published:2025-03-29
  • Contact: Liang Xuezhen, MD, Associate professor, Master’s supervisor, First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China; Department of Orthopaedic Microsurgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China
  • About author:Zhang Bochun, MS, First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82074453 (to LG); National Natural Science Foundation of China (Youth Project), No. 82205154 (to LXZ); Shandong Natural Science Foundation (Youth Project), No. ZR2021QH004 (to LXZ); Shandong Natural Science Foundation of China (General Project), No. ZR2024MH156 (to LXZ) 

摘要:


文题释义:
孟德尔随机化:使用遗传变异来评估暴露与结果之间的因果关系,类似于随机对照研究,是近年来非常流行的一种流行病学分析方法。孟德尔随机化除了能避免环境暴露等不相关的混杂因素外,还可以减轻反向因果关系的影响,提高因果推断的准确性。
骨坏死:是一种常见的难治性骨科疾病,病因广泛,发病机制尚不清楚,目前已经探索的潜在致病因素包括创伤、长期酗酒、激素用药史、镰状细胞贫血等。

背景:随着对骨坏死发病机制的不断探索研究,越来越多的研究证据显示神经影像学变化与骨坏死的发病存在密切联系,然而神经影像学变化与骨坏死的具体因果关联尚不明确。
目的:采用孟德尔随机化评估神经影像学指标与骨坏死之间的因果联系。
方法:神经影像学数据来自英国的UK Biobank数据库,该数据共纳入36 778名个体;骨坏死数据来自芬兰的FinnGen 数据库,包括1 543 例病例和391 037例对照。从结局因子中提取筛选出工具变量,进行两样本孟德尔随机化分析,通过逆方差加权法、MR-Egger、加权中位数法、简单模型法和加权模型法对数据进行分析,以逆方差加权法为主要分析方法,其余4种方法作为补充。为了验证数据的可行性和稳定性,对结果进行了敏感性分析。基于因果推断的复杂性,进一步进行了反向孟德尔随机化分析,以评估潜在的反向因果关系。
结果与结论:①逆方差加权分析结果显示,97种神经影像学数据与骨坏死正相关(P < 0.05,OR > 1),2种数据具有异质性,6种数据具有水平多效性;95种神经影像学表型与骨坏死呈负相关(P < 0.05,OR < 1),5种数据具有异质性,9种数据具有水平多效性;有2组数据具有反向因果关系。②采用两样本孟德尔随机化分析在学术界确立了神经影像学指标与骨坏死之间的因果联系,这些来自英国、芬兰的大样本数量为骨坏死病理生理学提供了新的理论基础,也为中国骨坏死的预测、筛查、早期诊断和预后提供可借鉴的思路和方法,有利于提高对骨坏死的临床诊断准确性和治疗的有效性。
https://orcid.org/0009-0008-4646-6953(张博淳)

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 神经影像学, 骨坏死, 因果关系, 孟德尔随机化, 工程化组织构建

Abstract: BACKGROUND: With the continuous exploration of the pathogenesis of osteonecrosis, more and more research evidence shows that neuroimaging change is closely related to the onset of osteonecrosis. However, the specific causal relationship between neuroimaging change and osteonecrosis is still unclear.
OBJECTIVE: To evaluate the causal relationship between neuroimaging indices and osteonecrosis using Mendelian Randomization analysis.
METHODS: Neuroimaging data were obtained from the UK Biobank database in the UK, which included a total of 36 778 individuals. Osteonecrosis data were obtained from the FinnGen database in Finland, including 1 543 cases and 391 037 controls. Instrumental variables were extracted and screened from outcome factors, and two-sample Mendelian randomization analysis was performed. The data were analyzed by inverse variance weighted method, MR-Egger, weighted median method, simple model method, and weighted model method. The inverse variance weighted method was used as the main analysis method, and the other four methods were used as supplements. To verify the feasibility and stability of the data, sensitivity analysis of the results was performed. Based on the complexity of causal inference, a reverse Mendelian randomization analysis was further performed to evaluate the potential reverse causal relationship.
RESULTS AND CONCLUSION: (1) The results of inverse variance weighted analysis showed that 97 neuroimaging data were positively correlated with osteonecrosis (P < 0.05, OR > 1); 2 data were heterogeneous and 6 data had horizontal pleiotropy. 95 neuroimaging phenotypes were negatively correlated with osteonecrosis (P < 0.05, OR < 1); 5 data were heterogeneous, and 9 data had horizontal pleiotropy; 2 groups of data had reverse causal relationships. (2) The two-sample Mendelian randomization analysis established the causal relationship between neuroimaging indicators and osteonecrosis in the academic community. These large sample numbers from the UK and Finland provide a new theoretical basis for the pathophysiology of osteonecrosis, and also provide ideas and methods for the prediction, screening, early diagnosis and prognosis of osteonecrosis in China, which is conducive to improving the accuracy of clinical diagnosis and the effectiveness of treatment of osteonecrosis.

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

Key words: neuroimaging, osteonecrosis, causality, Mendelian randomization, engineered tissue construction

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