Wang Zehui, Chen Tian, Shi Hongshuo, Zhang Xuecheng, Yang Wei
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai China.
China-Japan Friendship Hospital Beijing China.
Health Sci Rep. 2025 May 29;8(6):e70803. doi: 10.1002/hsr2.70803. eCollection 2025 Jun.
The link between circulating inflammatory proteins and perianal abscess remains uncertain. This study utilized the Mendelian randomization approach to examine the potential causality of 91 circulating inflammatory proteins in relation to perianal abscess (PA) and assessed the bidirectionality of these causal effects.
We conducted analyses using Genome-wide Association Studies (GWAS) summary statistics for 91 circulating inflammatory proteins, sourced from 11 cohorts with a combined total of 14,824 participants. Genetic associations for PA were taken from the FinnGen Consortium R9 data, consisting of 2595 PA cases and 301,931 control individuals. Two-sample Mendelian randomization (MR) analysis was utilized to investigate the causal links between these inflammatory proteins and PA. To validate the reliability of our MR findings, sensitivity analyses were carried out. Furthermore, reverse Mendelian randomization was employed to assess whether there is evidence for a reciprocal causal effect.
Employing the inverse-variance weighted (IVW) approach, our findings identified 7 circulating inflammatory proteins with a potential causal link to PA. Notably, increased levels of interleukin-18 receptor 1 (OR = 1.10, 95% CI 1.01-1.19, = 0.039), interleukin-33 (OR = 1.31, 95% CI 1.10-1.56, = 0.002), interleukin-7 (OR = 1.32, 95% CI 1.06-1.64, = 0.014), and tumor necrosis factor ligand superfamily member 12 (OR = 1.16, 95% CI 1.01-1.32, = 0.032) showed associations with increased risk for PA. Conversely, higher levels of T-cell surface glycoprotein CD6 isoform (OR = 0.81, 95% CI 0.68-0.98, = 0.026), interleukin-2 (OR = 0.80, 95% CI 0.66-0.97, = 0.026), and programmed cell death 1 ligand 1 (OR = 0.84, 95% CI 0.70-1.00, = 0.047) appeared to have protective effects against this condition. Additionally, our analysis has not found any evidence to suggest a reverse causal relationship between PA and the 7 specific inflammatory factors studied.
Our Mendelian randomization analysis identifies a probable causal association involving 91 circulating inflammatory proteins and the risk of PA development.
循环炎症蛋白与肛周脓肿之间的联系尚不确定。本研究采用孟德尔随机化方法，研究91种循环炎症蛋白与肛周脓肿（PA）之间的潜在因果关系，并评估这些因果效应的双向性。
我们使用了来自11个队列、总计14824名参与者的91种循环炎症蛋白的全基因组关联研究（GWAS）汇总统计数据进行分析。PA的基因关联数据取自芬兰基因组联盟R9数据，包括2595例PA病例和301931名对照个体。采用两样本孟德尔随机化（MR）分析来研究这些炎症蛋白与PA之间的因果联系。为验证我们MR结果的可靠性，进行了敏感性分析。此外，采用反向孟德尔随机化来评估是否有证据支持反向因果效应。
采用逆方差加权（IVW）方法，我们的研究结果确定了7种与PA有潜在因果联系的循环炎症蛋白。值得注意的是，白细胞介素-18受体1水平升高（OR = 1.10，95%CI 1.01-1.19，P = 0.039）、白细胞介素-33（OR = 1.31，95%CI 1.10-1.56，P = 0.002）、白细胞介素-7（OR = 1.32，95%CI 1.06-1.64，P = 0.014）和肿瘤坏死因子配体超家族成员12（OR = 1.16，95%CI 1.01-1.32，P = 0.032）与PA风险增加相关。相反，较高水平的T细胞表面糖蛋白CD6亚型（OR = 0.81，95%CI 0.68-0.98，P = 0.026）、白细胞介素-2（OR = 0.80，95%CI 0.66-0.97，P = 0.026）和程序性细胞死亡1配体1（OR = 0.84，95%CI 0.70-1.00，P = 0.047）似乎对这种情况有保护作用。此外，我们的分析未发现任何证据表明PA与所研究的7种特定炎症因子之间存在反向因果关系。
我们的孟德尔随机化分析确定了91种循环炎症蛋白与PA发生风险之间可能存在因果关联。
