He Tian, Fang Xi, Hu Xiao, Chen Cong, Zhang Peng, Ge Man, Xu Yi-Qing, Gao Zhao-Xing, Wang Peng, Wang De-Guang, Pan Hai-Feng
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Institute of Kidney Disease, Inflammation and Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei, Anhui, China.
Int J Rheum Dis. 2024 Dec;27(12):e15430. doi: 10.1111/1756-185X.15430.
Although earlier observational studies have revealed a connection between human papillomavirus (HPV) infection and several autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), the exact causative mechanism underlying this association is still unknown.
This two-sample bidirectional MR study was conducted based on publicly released data from genome-wide association studies (GWAS). Our results were mainly derived from the inverse variance weighted (IVW) model, with the remaining three models also being calculated. The MR Steiger test was used to examine the correctness of our causal direction. Sensitivity analysis was performed using Mendelian randomized pleiotropy residual sum and outlier (MR-PRESSO), MR-Egger regression.
The IVW results showed that there was a positive causal association between HPV16 E7 protein and SLE (odds ratio (OR) = 1.075, 95% confidence interval (CI), 1.003-1.151, FDR-p = 0.04), however, there was a negative causal association between HPV18 E7 protein and SLE (OR = 0.884, 95% CI, 0.804-0.972, FDR-p = 0.02). No causal associations of HPV16 E7 protein and HPV18 E7 protein with RA, IBD was observed including its subtypes Ulcerative colitis (UC) and Crohn's disease (CD). Sensitivity analysis showed that there was no significant heterogeneity (p > 0.05) or genetic pleiotropy (p > 0.05).
Our two-sample bidirectional Mendelian randomization study identifies a causal association between HPV infection and SLE, but no causal association between HPV infection and RA and IBD.
尽管早期的观察性研究已经揭示了人乳头瘤病毒（HPV）感染与几种自身免疫性疾病之间的联系，如系统性红斑狼疮（SLE）和类风湿性关节炎（RA），但这种关联背后的确切致病机制仍然未知。
这项两样本双向孟德尔随机化研究是基于全基因组关联研究（GWAS）公开的数据进行的。我们的结果主要来自逆方差加权（IVW）模型，同时也计算了其余三种模型。采用孟德尔随机化斯特格检验来检验我们因果方向的正确性。使用孟德尔随机化多效性残差和异常值（MR-PRESSO）、MR-Egger回归进行敏感性分析。
IVW结果显示，HPV16 E7蛋白与SLE之间存在正向因果关联（优势比（OR）=1.075，95%置信区间（CI），1.003 - 1.151，FDR-p = 0.04），然而，HPV18 E7蛋白与SLE之间存在负向因果关联（OR = 0.884，95% CI，0.804 - 0.972，FDR-p = 0.02）没观察到HPV16 E7蛋白和HPV18 E7蛋白与RA、炎症性肠病（IBD）及其亚型溃疡性结肠炎（UC）和克罗恩病（CD）之间存在因果关联。敏感性分析表明，不存在显著的异质性（p > 0.05）或基因多效性（p > 0.05）。
我们的两样本双向孟德尔随机化研究确定了HPV感染与SLE之间存在因果关联，但HPV感染与RA和IBD之间不存在因果关联。
