血液代谢物与骨质疏松症的孟德尔随机化研究  

The causal relationship between blood metabolites and osteoporosis:A Mendelian randomization study

作　　者：高志杰 汪悦东 张志海 GAO Zhijie;WANG Yuedong;ZHANG Zhihai(The Second Clinical Medical School,Guangzhou University of Chinese Medicine,Guangzhou 510000,China;The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangdong Provincial Hospital of Chinese Medicine,Guangzhou 510000,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510000,China;The Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510000,China)

机构地区：[1]广州中医药大学第二临床医学院,广东广州510000 [2]广东省中医院,广东广州510000 [3]广州中医药大学第一附属医院,广东广州510000 [4]广州中医药大学第三附属医院,广东广州510000

出　　处：《中国骨质疏松杂志》2024年第8期1164-1168,1203,共6页Chinese Journal of Osteoporosis

基　　金：广东省中医药局面上项目(20241397);广州市荔湾区科技计划项目(20240612);国家自然科学基金(82374482)。

摘　　要：目的采用孟德尔随机化分析方法研究1400种血液代谢物与骨质疏松症发病风险的因果关系。方法获取1400种血液代谢物与骨质疏松症的全基因组关联研究数据,将单核苷酸多态性作为工具变量并选择敏感的SNPs进行分析。通过IVW、WM、MR-Egger回归法进行两样本孟德尔随机化分析,以OR值检验1400种血液代谢物与骨质疏松症之间的因果关系,并完成敏感性和多效性检验。结果6种血液代谢物与骨质疏松症显著相关,GCST90199879、GCST90200092、GCST90200368、GCST90200656、GCST90200664、GCST90200973与骨质疏松症的孟德尔随机化分析结果显示,IVW法的OR值分别为0.973(95%CI:0.954~0.991,P=0.004)、0.883(95%CI:0.805~0.968,P=0.008)、1.111(95%CI:1.030~1.197,P=0.006)、1.147(95%CI:1.038~1.267,P=0.007)、1.069(95%CI:1.022~1.119,P=0.004)、0.741(95%CI:0.602~0.914,P=0.005),表明血液代谢物与骨质疏松症之间存在因果关系。IVW(P>0.05)和MR-Egger回归(P>0.05)的Cochran Q检验表明SNPs并不存在异质性。MR-Egger法的egger_intercept和0差异没有统计学意义(P>0.05),SNPs不存在水平多效性。结论本研究提示了6种血液代谢物与骨质疏松症之间存在因果关系,这为探讨血液代谢物介导的骨质疏松症的发病机制提供了新的认知。Objective This study used Mendelian randomization analysis to investigate the causal relationship between 1400 blood metabolites and the risk of osteoporosis.Methods Genomewide association study data on 1400 blood metabolites and osteoporosis were obtained.Single nucleotide polymorphisms(SNPs)were used as instrumental variables for analysis.Two-sample Mendelian randomization analysis was performed using IVW,WM,and MR-Egger regression method to examine the causal relationship between the 1400 blood metabolites and osteoporosis.The sensitivity and multiplicity tests were conducted.Results Six blood metabolites were significantly associated with osteoporosis.Mendelian randomization analysis result showed that the IVW OR values for GCST90199879,GCST90200092,GCST90200368,GCST90200656,GCST90200664,and GCST90200973 were 0.973(95%CI:0.954-0.991,P=0.004),0.883(95%CI:0.805-0.968,P=0.008),1.111(95%CI:1.030-1.197,P=0.006),1.147(95%CI:1.038-1.267,P=0.007),1.069(95%CI:1.022-1.119,P=0.004),and 0.741(95%CI:0.602-0.914,P=0.005),respectively,indicating a causal relationship between blood metabolites and osteoporosis.Cochran Q tests for IVW(P>0.05)and MR-Egger regression(P>0.05)indicated no heterogeneity in the SNPs.The Egger intercept of the MR-Egger method showed no significant statistical difference from 0(P>0.05),indicating no horizontal pleiotropy in the SNPs.Conclusion This study suggests a causal relationship between 6 blood metabolites and osteoporosis,providing new insights into the pathogenesis of osteoporosis mediated by blood metabolites.

关 键 词：骨质疏松症 血液代谢物 孟德尔随机化 因果关系 

分 类 号：R589.5[医药卫生—内分泌] R552[医药卫生—内科学]