Association of Polygenic Risk Scores With Radiographic Progression in Patients With Rheumatoid Arthritis
Association of Polygenic Risk Scores With Radiographic Progression in Patients With Rheumatoid Arthritis
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DOI：
10.1002/art.42051
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发表时间：
2022-03-24
影响因子：
13.3
通讯作者：
Kochi, Yuta
中科院分区：
文献类型：
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作者：
Honda, Suguru;Ikari, Katsunori;Kochi, Yuta
目的探讨类风湿关节炎（RA）易感性的全基因组关联研究（GWAS）数据获得的多基因风险评分是否可以作为影像学进展的预测指标。方法利用GWAS汇总数据构建多基因风险评分，分析单核苷酸多态性与类风湿关节炎易感性的关系。根据显著性水平将多基因风险评分分层为五分位数（从多基因风险评分的前五分位数到后五分位数）。此外，评估了RA发病后5年内影像学进展的Sharp/van der Heijde评分（SHS）的变化。5年内SHS的变化按四分位数分层，SHS变化的前四分位数定义为严重的放射学进展（评分变化bbbb35分），其余3个四分位数定义为非严重的放射学进展。在一个训练集（n = 500 RA患者）和一个测试集（n = 740 RA患者）中，评估多基因风险评分在5年内预测SHS状态的能力，以选择最佳模型，并对数据进行验证。我们在单变量和包含其他因素的多变量分析中评估了多基因风险评分作为严重影像学进展的预测指标的表现。结果在训练组（P = 0.0064）和测试组（P = 0.017）中，由43,784个单核苷酸多态性构建的多基因风险评分在经历严重放射学进展的患者和非严重放射学进展的患者之间存在显著差异。多基因风险评分在前五分位数的患者与多基因风险评分在后五分位数的患者相比，严重进展的风险更高（比值比[OR] 1.90, P = 0.0022），当限于发病时较年轻的患者时，严重放射学进展的风险甚至更高（OR 5.06, P = 0.00038）。多基因风险评分最高的五分之一组和抗瓜氨酸蛋白抗体（ACPA）阳性组的严重放射学进展患者比例显著高于其他组（P = 0.00052和P = 0.0022）。多因素分析显示，多基因风险评分（P = 0.00019）、女性性别（P = 0.0033）、ACPA阳性（P = 0.0023）、体重指数（P = 0.024）是严重影像学进展的独立危险因素。结论：基于GWAS数据的RA易感性多基因风险评分与RA患者放射学进展的严重程度相关。
Objective To investigate whether polygenic risk scores obtained using data from a genome-wide association study (GWAS) of rheumatoid arthritis (RA) susceptibility can be predictors of radiographic progression. Methods We constructed polygenic risk scores using GWAS summary data on associations of single-nucleotide polymorphisms with RA susceptibility. The polygenic risk scores were stratified into quintiles based on levels of significance (ranging from top quintile of polygenic risk scores to bottom quintile). In addition, change in the Sharp/van der Heijde score (SHS) of radiographic progression over the first 5 years after onset of RA was assessed. The change in SHS over 5 years was stratified according to quartiles, with the top quartile of change in SHS defined as severe radiographic progression (score change of >35 points) and the remaining 3 quartiles defined as nonsevere radiographic progression. Polygenic risk scores were assessed for their ability to predict the SHS status over 5 years in a training set (n = 500 RA patients) for selection of the best model, and in a testing set (n = 740 RA patients) for validation of the data. We evaluated the performance of the polygenic risk score as a predictor of severe radiographic progression in univariable and multivariable analyses with inclusion of other factors. Results Polygenic risk scores constructed from 43,784 single-nucleotide polymorphisms significantly differed between patients who experienced severe radiographic progression and those with nonsevere radiographic progression in both the training set (P = 0.0064) and the testing set (P = 0.017). Patients with polygenic risk scores in the top quintile had a higher risk of severe progression compared to those with polygenic risk scores in the bottom quintile (odds ratio [OR] 1.90, P = 0.0022), and the risk of severe radiographic progression was even higher when restricted to patients who were younger at disease onset (OR 5.06, P = 0.00038). The group with polygenic risk scores in the top quintile and the anti-citrullinated protein antibody (ACPA)-positive group had significantly higher proportions of patients with severe radiographic progression (P = 0.00052 and P = 0.0022, respectively) compared to the remaining groups. Multivariable analysis showed that polygenic risk score (P = 0.00019) as well as female sex (P = 0.0033), ACPA positivity (P = 0.0023), and body mass index (P = 0.024) were independent risk factors for severe radiographic progression. Conclusion A polygenic risk score that is derived from GWAS data on RA susceptibility is associated with the level of severity of radiographic progression in patients with RA.