Polygenic risk scores for rheumatoid arthritis and idiopathic pulmonary fibrosis and associations with RA, interstitial lung abnormalities, and quantitative interstitial abnormalities among smokers

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism Pub Date : 2025-03-15 DOI:10.1016/j.semarthrit.2025.152708

Gregory C McDermott , Matthew Moll , Michael H Cho , Keigo Hayashi , Pierre-Antoine Juge , Tracy J Doyle , Misti L Paudel , Gregory L Kinney , Vanessa L Kronzer , John S Kim , Lauren A O'Keeffe , Natalie A Davis , Elana J Bernstein , Paul F Dellaripa , Elizabeth A Regan , Gary M Hunninghake , Edwin K Silverman , Samuel Y Ash , Raul San Jose Estepar , George R Washko , Jeffrey A Sparks

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引用次数: 0

Abstract

Objective

Genome-wide association studies (GWAS) facilitate construction of polygenic risk scores (PRSs) for rheumatoid arthritis (RA) and idiopathic pulmonary fibrosis (IPF). We investigated associations of RA and IPF PRSs with RA and high-resolution chest computed tomography (HRCT) parenchymal lung abnormalities.

Methods

Participants in COPDGene, a prospective multicenter cohort of current/former smokers, had chest HRCT at study enrollment. Using genome-wide genotyping, RA and IPF PRSs were constructed using GWAS summary statistics. HRCT imaging underwent visual inspection for interstitial lung abnormalities (ILA) and quantitative CT (QCT) analysis using a machine-learning algorithm that quantified percentage of normal lung, interstitial abnormalities, and emphysema. RA was identified through self-report and DMARD use. We investigated associations of RA and IPF PRSs with RA, ILA, and QCT features using multivariable logistic and linear regression.

Results

We analyzed 9,230 COPDGene participants (mean age 59.6 years, 46.4 % female, 67.2 % non-Hispanic White, 32.8 % Black/African American). In non-Hispanic White participants, RA PRS was associated with RA diagnosis (OR 1.32 per unit, 95 %CI 1.18–1.49) but not ILA or QCT features. Among non-Hispanic White participants, IPF PRS was associated with ILA (OR 1.88 per unit, 95 %CI 1.52–2.32) and quantitative interstitial abnormalities (adjusted β=+0.50 % per unit, p = 7.3 × 10⁻⁸) but not RA. There were no statistically significant associations among Black/African American participants.

Conclusions

RA and IPF PRSs were associated with their intended phenotypes among non-Hispanic White participants but performed poorly among Black/African American participants. PRS may have future application to risk stratify for RA diagnosis among patients with ILD or for ILD among patients with RA.

查看原文本刊更多论文

吸烟者类风湿关节炎和特发性肺纤维化的多基因风险评分及其与类风湿关节炎、肺间质异常和定量间质异常的关系

目的全基因组关联研究（GWAS）有助于类风湿关节炎（RA）和特发性肺纤维化（IPF）多基因风险评分（prs）的构建。我们研究了RA和IPF PRSs与RA和高分辨率胸部计算机断层扫描（HRCT）肺实质异常的关系。COPDGene是一项前瞻性多中心队列研究，参与者在入组时接受胸部HRCT检查。采用全基因组分型，利用GWAS汇总统计构建RA和IPF PRSs。HRCT成像通过视觉检查肺间质异常（ILA）和定量CT （QCT）分析，使用机器学习算法量化正常肺、间质异常和肺气肿的百分比。RA通过自我报告和使用DMARD来确定。我们使用多变量逻辑回归和线性回归研究了RA和IPF PRSs与RA、ILA和QCT特征的关系。结果我们分析了9230名COPDGene参与者（平均年龄59.6岁，46.4%为女性，67.2%为非西班牙裔白人，32.8%为黑人/非洲裔美国人）。在非西班牙裔白人参与者中，RA PRS与RA诊断相关（OR为1.32 /单位，95% CI为1.18-1.49），但与ILA或QCT特征无关。在非西班牙裔白人参与者中，IPF PRS与ILA （OR 1.88 /单位，95% CI 1.52-2.32）和定量间质异常（调整后的β=+ 0.50% /单位，p = 7.3 × 10 - 8）相关，但与RA无关。在黑人/非裔美国人参与者中没有统计学上的显著关联。结论ra和IPF PRSs在非西班牙裔白人参与者中与其预期表型相关，但在黑人/非裔美国人参与者中表现不佳。PRS可能在未来应用于ILD患者的RA诊断或RA患者的ILD的风险分层。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Seminars in arthritis and rheumatism 医学-风湿病学

CiteScore

9.20

自引率

4.00%

发文量

176

审稿时长

46 days

期刊介绍： Seminars in Arthritis and Rheumatism provides access to the highest-quality clinical, therapeutic and translational research about arthritis, rheumatology and musculoskeletal disorders that affect the joints and connective tissue. Each bimonthly issue includes articles giving you the latest diagnostic criteria, consensus statements, systematic reviews and meta-analyses as well as clinical and translational research studies. Read this journal for the latest groundbreaking research and to gain insights from scientists and clinicians on the management and treatment of musculoskeletal and autoimmune rheumatologic diseases. The journal is of interest to rheumatologists, orthopedic surgeons, internal medicine physicians, immunologists and specialists in bone and mineral metabolism.