Liu Chang, Ma Zhijun, Zhao Xin, Luo Fang, Li Huinan, Shen Dingkun, Zhou Wei, Cao Puhua, Su Chengguo, Zhu Jun
School of Acupuncture-Moxibustion and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China.
Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Medicine (Baltimore). 2025 Jan 31;104(5):e41397. doi: 10.1097/MD.0000000000041397.
Previous observational studies have suggested an association between antibiotic use and rheumatoid arthritis (RA), though the causal relationship remains unclear. This study aimed to investigate the causal link between antibiotic use and RA in a European population using Mendelian randomization (MR). We utilized pooled genome-wide association study (GWAS) data on 12 antibiotics and RA from European populations, extracted from the GWAS Catalog. Both univariate MR and multivariate MR were employed to examine the causal relationship. Three analysis methods were applied: inverse variance weighting, MR-Egger, and weighted median, with inverse variance weighting as the primary method. Sensitivity analyses were conducted using Cochran Q statistics, MR-PRESSO, the MR-Egger intercept, and the leave-one-out test. Univariate MR revealed that tetracycline use was positively associated with RA (odds ratio = 1.013, 95% confidence interval = 1.001-1.024, P = .028), while none of the other 11 antibiotics exhibited a causal relationship with RA. However, further multivariate MR analysis found no causal association between tetracycline use and RA. Our results do not support a direct causal relationship between RA and antibiotic use, which may help alleviate some concerns among clinicians. Further MR studies are needed to validate these findings as additional datasets from other cohorts and GWASs with more detailed information become available.
先前的观察性研究表明抗生素使用与类风湿性关节炎(RA)之间存在关联,但其因果关系仍不明确。本研究旨在利用孟德尔随机化(MR)方法调查欧洲人群中抗生素使用与RA之间的因果联系。我们使用了从GWAS目录中提取的欧洲人群关于12种抗生素和RA的汇总全基因组关联研究(GWAS)数据。采用单变量MR和多变量MR来检验因果关系。应用了三种分析方法:逆方差加权法、MR-Egger法和加权中位数法,以逆方差加权法作为主要方法。使用Cochran Q统计量、MR-PRESSO、MR-Egger截距和留一法检验进行敏感性分析。单变量MR显示,使用四环素与RA呈正相关(优势比 = 1.013,95%置信区间 = 1.001 - 1.024,P = 0.028),而其他11种抗生素均未显示与RA存在因果关系。然而,进一步的多变量MR分析发现,使用四环素与RA之间不存在因果关联。我们的结果不支持RA与抗生素使用之间存在直接因果关系,这可能有助于减轻临床医生的一些担忧。随着来自其他队列和具有更详细信息的GWAS的更多数据集可用,需要进一步的MR研究来验证这些发现。