Luo Pan, Cheng Shiqiang, Zhang Feng, Feng Ruoyang, Xu Ke, Jing Wensen, Xu Peng
Department of Joint Surgery, HongHui Hospital, Xi'an Jiaotong University, Xi'an, China.
Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
Bone Joint Res. 2022 Feb;11(2):134-142. doi: 10.1302/2046-3758.112.BJR-2021-0270.R1.
The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA).
Based on the genome-wide association studies (GWAS) summary statistics of RA from European descent and the GWAS summary datasets of 3,622 plasma proteins, we explored the relationship between RA and plasma proteins from three aspects. First, linkage disequilibrium score regression (LD score regression) was applied to detect the genetic correlation between RA and plasma proteins. Mendelian randomization (MR) analysis was then used to evaluate the causal association between RA and plasma proteins. Finally, GEO2R was used to screen the differentially expressed genes (DEGs) between patients with RA and healthy controls.
We found that seven kinds of plasma proteins had genetic correlations with RA, such as Soluble Receptor for Advanced Glycation End Products (sRAGE) (correlation coefficient = 0.2582, p = 0.049), vesicle transport protein USE1 (correlation coefficient = 0.1337, p = 0.018), and spermatogenesis-associated protein 20 (correlation coefficient = 0.3706, p = 0.018). There was a significant causal relationship between sRAGE and RA. By comparing the genes encoding seven plasma proteins, we found that only USE1 was a DEG associated with RA.
Our study identified a set of candidate plasma proteins that showed signals correlated with RA. Since the results of this study need further experimental verification, they should be interpreted with caution. However, we hope that this paper will provide new insights for the discovery of pathogenic genes and RA pathogenesis in the future. Cite this article: 2022;11(2):134-142.
本研究旨在探讨血浆蛋白与类风湿关节炎（RA）之间的遗传相关性及因果关系。
基于欧洲血统人群类风湿关节炎的全基因组关联研究（GWAS）汇总统计数据以及3622种血浆蛋白的GWAS汇总数据集，我们从三个方面探讨了RA与血浆蛋白之间的关系。首先，应用连锁不平衡评分回归（LD score regression）检测RA与血浆蛋白之间的遗传相关性。然后采用孟德尔随机化（MR）分析评估RA与血浆蛋白之间的因果关联。最后，使用GEO2R筛选RA患者与健康对照之间的差异表达基因（DEG）。
我们发现七种血浆蛋白与RA存在遗传相关性，如晚期糖基化终产物可溶性受体（sRAGE）（相关系数 = 0.2582，p = 0.049）、囊泡运输蛋白USE1（相关系数 = 0.1337，p = 0.018）和精子发生相关蛋白20（相关系数 = 0.3706，p = 0.018）。sRAGE与RA之间存在显著的因果关系。通过比较编码七种血浆蛋白的基因，我们发现只有USE1是与RA相关的差异表达基因。
我们的研究确定了一组与RA相关的候选血浆蛋白。由于本研究结果需要进一步实验验证，应谨慎解读。然而，我们希望本文能为未来致病基因的发现及RA发病机制的研究提供新的见解。引用本文：2022;11(2):134 - 142。
