[1]张云辉,郭慧,朱瑞征,等.肠道菌群与膝骨关节炎因果关系的双向孟德尔随机化分析[J].中医正骨,2024,36(12):32-42.
　ZHANG Yunhui,GUO Hui,ZHU Ruizheng,et al.Investigation on the causal relationship between gut microbiota and knee osteoarthritis:a bidirectional mendelian randomization analysis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2024,36(12):32-42.
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肠道菌群与膝骨关节炎因果关系的双向孟德尔随机化分析()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第36卷
期数:
2024年12期
页码:
32-42
栏目:
数据库研究
出版日期:
2024-12-20

文章信息/Info

Title:
Investigation on the causal relationship between gut microbiota and knee osteoarthritis:a bidirectional mendelian randomization analysis
作者:
张云辉1; 郭慧1; 朱瑞征1; 王莹1; 唐广君1; 莫星杰2; 陈少佳2; 陈兆军1
1.北京中医药大学第三附属医院,北京 100029; 2.北京中医药大学第三临床医学院,北京 100029
Author(s):
ZHANG Yunhui1; GUO Hui1; ZHU Ruizheng1; WANG Ying1; TANG Guangjun1; MO Xingjie2; CHEN Shaojia2; CHEN Zhaojun1
1.The Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine,Beijing 100029,China 2.The Third Clinical Medical College of Beijing University of Traditional Chinese Medicine,Beijing 100029,China
关键词:
骨关节炎; 膝;  胃肠道微生物群;  孟德尔随机化分析;  全基因组关联研究
Keywords:
osteoarthritis; knee;  gastrointestinal microbiome;  Mendelian randomization analysis;  genome-wide association study
摘要:
目的:探讨肠道菌群与膝骨关节炎(knee osteoarthritis,KOA)的因果关系。方法:分别从MiBioGen和IEU OpenGWAS project数据库中筛选获得肠道菌群的全基因组关联研究(genome-wide association study,GWAS)数据集和KOA的GWAS数据集。在分析工具R包中从肠道菌群的GWAS数据集中筛选符合要求的单核苷酸多态性(single nucleotide polymorphism,SNP)位点作为工具变量,根据筛选出的工具变量从KOA数据集中匹配相应的SNP位点。采用逆方差加权法、加权模式、简单模式、加权中位数和孟德尔随机化(Mendelian randomization,MR)-Egger回归法进行MR分析。采用MR-Egger截距检验检测水平多效性。采用Cochran's Q检验评估MR-Egger和逆方差加权法分析结果的异质性。采用MR-Steiger方向性检验判断2个变量之间是否存在显著的线性趋势。采用留一法评估MR分析结果的稳定性。以KOA的SNP位点作为工具变量,以正向MR分析中逆方差加权法所确定的与KOA存在因果关联的肠道菌群作为结局进行反向MR分析。结果:共筛选144个肠道菌群的SNP位点作为工具变量,F值范围为15.064～25.838; 共筛选11个KOA的SNP位点作为工具变量,F值范围为19.102～35.742。正向MR分析结果显示,布劳特氏菌属、阿德勒菌属和土孢杆菌属与KOA发生风险呈负相关。MR-Egger截距检验和Cochran's Q检验结果显示,肠道菌群与KOA的因果关系均不存在水平多效性和异质性。MR-Steiger方向性检验结果表明,从肠道菌群到膝关节炎的方向上是稳健的。留一法检验结果显示,不存在对肠道菌群与KOA的因果关系造成严重影响的SNP位点,MR分析结果稳健。反向MR分析结果显示肠道菌群与KOA不存在反向因果关系。结论:布劳特氏菌属、阿德勒菌属及土孢杆菌属可能是对降低KOA风险有益的肠道菌群,这可作为通过肠道菌群干预KOA研究的线索和方向。
Abstract:
Objective:To investigate the causal relationship between gut microbiota(GM)and knee osteoarthritis(KOA).Methods:The genome-wide association study(GWAS)datasets about GM and KOA were extracted from the MiBioGen database and IEU OpenGWAS project database,respectively.The eligible single nucleotide polymorphism(SNP)loci were screened as instrumental variables from the GM GWAS datasets,and the SNP loci matched with the instrumental variables were selected from the KOA GWAS datasets in the analysis tool R package.After that,a mendelian randomization(MR)analysis was conducted by using inverse variance weighted(IVW),weighted mode(WM),simple mode(SM),weighted median estimator(WME)and MR-Egger regression.The horizontal pleiotropy was examined by MR-Egger intercept test,and Cochran's Q test was performed on the heterogeneity of the results analyzed by IVW method and MR-egger me-thod.MR-Steiger directionality test was performed to judge whether there was obvious linear trend between the two variables.In addition,the stability of the MR analysis results was evaluated by leave-one-out(LOO)test.Furthermore,a reverse MR analysis was conducted by taking the screened KOA SNP loci as instrumental variable,and the GM having a reliable causal relationship to KOA obtained from the IVW forward MR analysis as the outcome variable.Results:One hundred and forty-four GM SNP loci and 11 KOA SNP loci were included and served as the instrumental variables(F value of 15.064-25.838 and 19.102-35.742).The results of forward MR analysis showed an inverse causal relationship between GM(including genus blautia,genus adlercreutzia and genus terrisporonacter)and KOA.The results of MR-Egger intercept test and Cochran's Q test indicated that there was no horizontal pleiotropy and heterogeneity in the causal relationship between GM and KOA.MR-Steiger directionality test results showed a stable and reliable direction from GM to KOA.The results of LOO test showed none of SNP loci could bring a serious impact on the causal relationship between GM and KOA,indicating a stable and reliable MR analysis result.The reverse MR analysis results showed there was no reverse causal relationship between GM and KOA.Conclusion:Genus blautia,genus adlercreutzia and genus terrisporonacter may be the GM which is beneficial to reduce the risk of KOA,and it can provide the clues and directions for the research on intervention of KOA via GM.

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备注/Memo

备注/Memo:
基金项目:首都卫生发展科研专项项目(2022-2-7033); 北京中医药大学第三附属医院“新药研发”培育项目(BZYSY-2022-XYYF-22)
通讯作者:陈兆军 E-mail:zhaojunchen66@126.com
更新日期/Last Update: 1900-01-01