强直性脊柱炎与人工关节置换术后假体机械 并发症的因果关系：双样本孟德尔随机研究

Causal Relationship between Ankylosing Spondylitis and Prosthetic Mechanical Complications after Joint Arthroplasty: A Two-Sample Mendelian Randomization Study

摘要: 目的：本研究旨在探讨强直性脊柱炎(AS)与人工关节置换术后假体机械并发症之间的因果关系，以期临床医生在手术时采取可能的预防措施。方法：采用双样本孟德尔随机化(MR)分析，以单核苷酸多态性(SNP)为工具变量，从IEU GWAS数据库获取欧洲血统个体的暴露和结局数据。共选取42个与AS相关的全基因组显著且独立的SNP，经筛选后对38个SNP进行MR分析。使用逆方差加权(IVW)法评估AS对假体机械并发症的因果效应，并采用MR-Egger、加权中值、简单模式、加权模式等方法进行敏感性分析，以检测异质性、水平多效性和离群值。结果：基于IVW法，AS与假体机械并发症存在因果关系，AS会增加其发生率(OR = 1.037, 95% CI = 1.011~1.062; P = 0.00366)。Cochran Q检验显示SNP之间无显著异质性(Q = 36.267, P = 0.503)，MR-Egger截距评价显示本研究中不存在水平多效性证据(MR-Egger截距 = 1.119 × 10⁻⁴；SE = 5.5673 × 10⁻⁵；P = 0.052)，MR-PRESSO检验表明本研究不存在离群值和水平多向性，leave-one-out检验结果证明，排除任何单个SNP后，AS对假体机械并发症的因果效应没有显著波动。敏感性分析未发现异质性或水平多效性，结果稳定可靠。结论：本研究为AS患者关节置换术后假体机械并发症风险增加提供了因果证据，提示临床医生在手术时需考虑适当的预防措施。

Abstract: Objective: The purpose of this study was to investigate the causal relationship between ankylosing spondylitis (AS) and mechanical complications of prostheses after artificial joint replacement, with a view to possible preventive measures for clinicians during surgery. Methods: Two-sample Mendelian randomization (MR) analysis was used to obtain exposure and outcome data of European ancestry individuals from IEU GWAS database with single nucleotide polymorphism (SNP) as the instrumental variable. A total of 42 genome-wide significant and independent SNPS associated with AS were selected, and 38 SNPS were screened for MR Analysis. Inverse variance weighting (IVW) method was used to evaluate the causal effect of AS on mechanical complications of prosthesis, and sensitivity analysis was performed using MR-Egger, weighted median, simple model, weighted model and other methods to detect heterogeneity, horizontal pleiotropy and outliers. Results: Based on IVW method, there was a causal relationship between AS and mechanical complications of prosthesis, and AS increased its incidence (OR = 1.037, 95% CI = 1.011~1.062; P = 0.00366). Cochran Q test showed no significant heterogeneity among SNPS (Q = 36.267, P = 0.503), and the MR-Egger intercept evaluation showed that there was no evidence of horizontal pleiotropy in this study (MR-Egger intercept = 1.119 × 10⁻⁴; SE = 5.5673 × 10⁻⁵; P = 0.052); MR-PRESSO test showed that there were no outliers and horizontal multidirectivity in this study, and leave-one-out test results proved that the causal effect of AS on mechanical complications of prosthesis did not significantly change after excluding any single SNP. No heterogeneity or horizontal pleiotropy was found in sensitivity analysis, and the results were stable and reliable. Conclusions: This study provides causal evidence for an increased risk of prosthesis mechanical complications after joint replacement in patients with AS, suggesting that clinicians should consider appropriate preventive measures during surgery.