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[1]張?jiān)戚x,郭慧,朱瑞征,等.腸道菌群與膝骨關(guān)節(jié)炎因果關(guān)系的雙向孟德爾隨機(jī)化分析[J].中醫(yī)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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腸道菌群與膝骨關(guān)節(jié)炎因果關(guān)系的雙向孟德爾隨機(jī)化分析()
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《中醫(yī)正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第36卷
期數(shù):
2024年12期
頁碼:
32-42
欄目:
數(shù)據(jù)庫研究
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:
張?jiān)戚x1; 郭慧1; 朱瑞征1; 王瑩1; 唐廣君1; 莫星杰2; 陳少佳2; 陳兆軍1
1.北京中醫(yī)藥大學(xué)第三附屬醫(yī)院,北京 100029; 2.北京中醫(yī)藥大學(xué)第三臨床醫(yī)學(xué)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
關(guān)鍵詞:
骨關(guān)節(jié)炎; 膝;  胃腸道微生物群;  孟德爾隨機(jī)化分析;  全基因組關(guān)聯(lián)研究
Keywords:
osteoarthritis; knee;  gastrointestinal microbiome;  Mendelian randomization analysis;  genome-wide association study
摘要:
目的:探討腸道菌群與膝骨關(guān)節(jié)炎(knee osteoarthritis,KOA)的因果關(guān)系。方法:分別從MiBioGen和IEU OpenGWAS project數(shù)據(jù)庫中篩選獲得腸道菌群的全基因組關(guān)聯(lián)研究(genome-wide association study,GWAS)數(shù)據(jù)集和KOA的GWAS數(shù)據(jù)集。在分析工具R包中從腸道菌群的GWAS數(shù)據(jù)集中篩選符合要求的單核苷酸多態(tài)性(single nucleotide polymorphism,SNP)位點(diǎn)作為工具變量,根據(jù)篩選出的工具變量從KOA數(shù)據(jù)集中匹配相應(yīng)的SNP位點(diǎn)。采用逆方差加權(quán)法、加權(quán)模式、簡(jiǎn)單模式、加權(quán)中位數(shù)和孟德爾隨機(jī)化(Mendelian randomization,MR)-Egger回歸法進(jìn)行MR分析。采用MR-Egger截距檢驗(yàn)檢測(cè)水平多效性。采用Cochran's Q檢驗(yàn)評(píng)估MR-Egger和逆方差加權(quán)法分析結(jié)果的異質(zhì)性。采用MR-Steiger方向性檢驗(yàn)判斷2個(gè)變量之間是否存在顯著的線性趨勢(shì)。采用留一法評(píng)估MR分析結(jié)果的穩(wěn)定性。以KOA的SNP位點(diǎn)作為工具變量,以正向MR分析中逆方差加權(quán)法所確定的與KOA存在因果關(guān)聯(lián)的腸道菌群作為結(jié)局進(jìn)行反向MR分析。結(jié)果:共篩選144個(gè)腸道菌群的SNP位點(diǎn)作為工具變量,F值范圍為15.064～25.838; 共篩選11個(gè)KOA的SNP位點(diǎn)作為工具變量,F值范圍為19.102～35.742。正向MR分析結(jié)果顯示,布勞特氏菌屬、阿德勒菌屬和土孢桿菌屬與KOA發(fā)生風(fēng)險(xiǎn)呈負(fù)相關(guān)。MR-Egger截距檢驗(yàn)和Cochran's Q檢驗(yàn)結(jié)果顯示,腸道菌群與KOA的因果關(guān)系均不存在水平多效性和異質(zhì)性。MR-Steiger方向性檢驗(yàn)結(jié)果表明,從腸道菌群到膝關(guān)節(jié)炎的方向上是穩(wěn)健的。留一法檢驗(yàn)結(jié)果顯示,不存在對(duì)腸道菌群與KOA的因果關(guān)系造成嚴(yán)重影響的SNP位點(diǎn),MR分析結(jié)果穩(wěn)健。反向MR分析結(jié)果顯示腸道菌群與KOA不存在反向因果關(guān)系。結(jié)論:布勞特氏菌屬、阿德勒菌屬及土孢桿菌屬可能是對(duì)降低KOA風(fēng)險(xiǎn)有益的腸道菌群,這可作為通過腸道菌群干預(yù)KOA研究的線索和方向。
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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備注/Memo

備注/Memo:
基金項(xiàng)目:首都衛(wèi)生發(fā)展科研專項(xiàng)項(xiàng)目(2022-2-7033); 北京中醫(yī)藥大學(xué)第三附屬醫(yī)院“新藥研發(fā)”培育項(xiàng)目(BZYSY-2022-XYYF-22)
通訊作者:陳兆軍 E-mail:[email protected]
更新日期/Last Update: 1900-01-01