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  

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

作　　者：张博淳 李威 李广政 丁浩秦 李刚[2] 梁学振 Zhang Bochun;Li Wei;Li Guangzheng;Ding Haoqin;Li Gang;Liang Xuezhen(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)

机构地区：[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

出　　处：《中国组织工程研究》2025年第30期6574-6582,共9页Chinese Journal of Tissue Engineering Research

基　　金：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。

摘　　要：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36778名个体;骨坏死数据来自芬兰的FinnGen数据库,包括1543例病例和391037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。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 36778 individuals.Osteonecrosis data were obtained from the FinnGen database in Finland,including 1543 cases and 391037 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 als

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 

分 类 号：R459.9[医药卫生—治疗学] R319[医药卫生—临床医学] R681