双样本孟德尔随机化分析肠道菌群与类风湿性关节炎的因果关系
投稿时间:2024-10-31  修订日期:2025-03-03  点此下载全文
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作者单位邮编
孔德策 上海市浦东新区公利医院 200135
张莲卿 海军军医大学第一附属医院药学部 200082
张小莉 武汉市第四医院
武汉市第四医院 
430000
张岩 上海市浦东新区公利医院 200135
王卓 海军军医大学第一附属医院药学部 200433
中文摘要:目的 利用孟德尔随机化(Mendelian randomization,MR)分析肠道菌群与类风湿性关节炎(Rheumatoid arthritis ,RA)之间的因果关系。方法 获取肠道菌群和RA的全基因组关联研究(genome-wide association study,GWAS)数据,筛选出强工具变量(Instrumental variable,IV) ,以逆方差加权法( Inverse-variance weighting,IVW)为主,Egger回归法(Mendelian Randomization Egger Regression,MR-Egger)等其他四种方法作为补充,评价因果效应;再使用Cochran Q、MR-PRESSO、MR-Egger截距检验和留一法对分析评估结果进行敏感性分析。结果 MR分析共鉴定出6种肠道菌群(LachnospiraceaeUCG001属、Flavonifracto属、CandidatusSoleaferrea属、Actinomyce属、Butyrivibrio属和Bifidobacterium属),均与RA的关联效应值差异具有统计学意义( P<0.05)。IVW:LachnospiraceaeUCG001属(OR:1.002;95%CI:1.000~1.004);Flavonifracto属(OR:1.003;95%CI:1.000~1.005);CandidatusSoleaferrea属(OR:1.002;95%CI:1.001~1.004)、Actinomyce属(OR:1.003;95%CI:1.001~1.006);Butyrivibrio属(OR:0.999;95%CI:0.998~1.000); Bifidobacterium属(OR:0.998;95%CI:0.996~1.000)。Cochran Q检验未发现异质性,MR-PRESSO检验未检出离群值,MR-Egger截距检验显示结果无水平多效性,留一法分析进一步支持结果的稳健性。结论 MR分析结果支持肠道菌群和RA存在潜在的因果关系,其中Actinomyce属、Flavonifracto属、Candidatus Soleaferrea属及Lachnospiraceae UCG001属是类风湿性关节炎的危险因素,而Bifidobacterium属和Butyrivibrio属则为保护因素。
中文关键词:肠道菌群  类风湿性关节炎  孟德尔随机化  因果关系  逆方差加权法
 
Analyze the causal relationship between gut microbiota and rheumatoide arthritis based using a two-sample Mendelian randomization
Abstract:Objective To analyze the causal relationship between gut microbiota and rheumatoid arthritis (RA) using Mendelian randomization (MR). Methods We obtained genome-wide association study (GWAS) data on gut microbiota and RA, screened out strong instrumental variables (IVs), and evaluated the causal effect primarily using inverse-variance weighting (IVW), supplemented by MR-Egger and other three methods. Sensitivity analyses were conducted using Cochran Q test, MR-PRESSO, MR-Egger intercept test, and leave-one-out method. Results Six gut microbial genera were identified with statistically significant associations with RA (P < 0.05): Lachnospiraceae UCG001, Flavonifracto, Candidatus Soleaferrea, Actinomyces, Butyrivibrio, and Bifidobacterium. IVW results: Lachnospiraceae UCG001 (OR: 1.002; 95%CI: 1.000–1.004); Flavonifracto (OR: 1.003; 95%CI: 1.000–1.005); Candidatus Soleaferrea (OR: 1.002; 95%CI: 1.001–1.004); Actinomyces (OR: 1.003; 95%CI: 1.001–1.006); Butyrivibrio (OR: 0.999; 95%CI: 0.998–1.000); Bifidobacteri
keywords:Gut microbiota  Rheumatoid arthritis  Mendelian randomization  Causal relationship  Inverse-variance weighting
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