Genome-wide polygenic risk score for rheumatoid arthritis prediction in postmenopausal women

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Gene Medicine Pub Date : 2024-01-08 DOI:10.1002/jgm.3659

Yingke Xu, Qing Wu

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Abstract

Background

Rheumatoid arthritis (RA), a common autoimmune disease, exhibits a vital genetic component. Polygenic risk scores (PRS) derived from genome-wide association studies (GWAS) offer potential utility in predicting disease susceptibility. The present study aimed to develop and validate a PRS for predicting RA risk in postmenopausal women.

Methods

The study developed a novel PRS using 225,000 genetic variants from a GWAS dataset. The PRS was developed in a cohort of 8967 postmenopausal women and validated in an independent cohort of 6269 postmenopausal women. Among the development cohort, approximately 70% were Hispanic and approximately 30% were African American. The testing cohort comprised approximately 50% Hispanic and 50% Caucasian individuals. Stratification according to PRS quintiles revealed a pronounced gradient in RA prevalence and odds ratios.

Results

High PRS was significantly associated with increased RA risk in individuals aged 60–70 years, ≥ 70 years, and overweight and obese participants. Furthermore, at age 65 years, individuals in the bottom 5% of the PRS distribution have an absolute risk of RA at 30.6% (95% confidence interval = 18.5%–42.6%). The risk increased to 53.8% (95% confidence interval = 42.8%–64.9%) for those in the top 5% of the PRS distribution.

Conclusions

The PRS developed in the present study is significantly associated with RA risk, showing the potential for early screening of RA in postmenopausal women. This work demonstrates the feasibility of personalized medicine in identifying high-risk individuals for RA, indicating the need for further studies to test the utility of PRS in other populations.

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用于预测绝经后妇女类风湿关节炎的全基因组多基因风险评分

背景类风湿性关节炎（RA）是一种常见的自身免疫性疾病，具有重要的遗传因素。从全基因组关联研究（GWAS）中得出的多基因风险评分（PRS）可用于预测疾病的易感性。本研究旨在开发并验证用于预测绝经后女性 RA 风险的 PRS。方法该研究利用 GWAS 数据集中的 225,000 个基因变异开发了一种新型 PRS。该PRS是在8967名绝经后妇女的队列中开发的，并在6269名绝经后妇女的独立队列中进行了验证。在开发队列中，约 70% 为西班牙裔，约 30% 为非裔美国人。测试队列中约有 50%为西班牙裔，50%为白种人。根据 PRS 五分位数进行的分层显示了 RA 患病率和几率的明显梯度。结果在 60-70 岁、≥ 70 岁以及超重和肥胖的参与者中，高 PRS 与 RA 风险的增加明显相关。此外，在 65 岁时，PRS 分布中最低 5%的人患 RA 的绝对风险为 30.6%（95% 置信区间 = 18.5%-42.6%）。而PRS分布前5%的人的风险则增加到53.8%（95%置信区间=42.8%-64.9%）。结论本研究开发的 PRS 与 RA 风险显著相关，显示了对绝经后妇女进行 RA 早期筛查的潜力。这项工作证明了个性化医疗在识别 RA 高危人群方面的可行性，表明有必要开展进一步研究，以测试 PRS 在其他人群中的实用性。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.