Qin Qian, Jiang Yong'An, Fan Hengyi, Yuan Raorao, Zhong Bo, Zhang Yichen, Zhang Zile, Lei Xin, Cai Jianhui, Cheng Shiqi
Department of Neurosurgery, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, P. R. China.
Nanchang University, Nanchang, 330006, Jiangxi, P. R. China.
Hereditas. 2025 Feb 14;162(1):23. doi: 10.1186/s41065-025-00386-8.
Rheumatoid arthritis (RA) increases the risk of stroke. However, the relationship between RA and stroke remains unclear. This study aimed to explore the shared genetics architecture (i.e., common genetic basis between different traits, diseases, or phenotypes) of RA and stroke, aiming to improve the intervention and management of patients with RA and stroke.
Pooled statistics from publicly available genome-wide association studies for RA (8,255 cases and 409,001 controls) and stroke (43,132 cases and 43,132 controls) were used. A genome-wide positive association was conducted to (examine the comprehensive effects of genetic variants on a particular trait, disease, or phenotype at the genome-wide scale). Local genetic correlation studies used linkage disequilibrium score regression and super genetic covariance analyzer. Single nucleotide polymorphisms (SNPs) at risk were identified using genome-wide association study multiple trait analysis and PLINK software (P <5e-08), followed by functional localization and annotation using Functional Mapping and Annotation of Genome-Wide Association Studies to identify specific genes and genetic variants that may contribute to the disease. Finally, a transcriptome-wide association study explored the relationship between genes and their association with RA risk.
A genome-wide significant positive correlation was evident between RA and stroke (genetic correlation = 0.3756). Among the localized genomic regions, the correlation between RA and stroke in the region of chr2:201572564-202,829,668 was the most significant (p = 0.0015). We identified 179 significant SNPs and five common risk genes for RA and stroke (IRF5, RNASET2, ZNF438, UBE2LS, and SYNGR1). These genes are involved in the immune-inflammatory pathway.
The findings suggest a shared genetic structure between RA and stroke. These findings may provide new insights into RA and stroke pathogenesis, and contribute to the development of new diagnostic markers and therapeutic targeted drugs to improve the clinical outcomes of patients with RA and stroke.
类风湿性关节炎（RA）会增加中风风险。然而，RA与中风之间的关系仍不明确。本研究旨在探索RA与中风的共同遗传结构（即不同性状、疾病或表型之间的共同遗传基础），以改善对RA和中风患者的干预与管理。
使用来自公开可用的全基因组关联研究的汇总统计数据，其中RA的研究有8255例病例和409,001例对照，中风的研究有43,132例病例和43,132例对照。进行全基因组阳性关联研究（以在全基因组范围内检查遗传变异对特定性状、疾病或表型的综合影响）。局部遗传相关性研究使用连锁不平衡评分回归和超级遗传协方差分析器。使用全基因组关联研究多性状分析和PLINK软件（P<5e-08）鉴定有风险的单核苷酸多态性（SNP），随后使用全基因组关联研究的功能图谱和注释进行功能定位和注释，以识别可能导致该疾病的特定基因和遗传变异。最后，进行全转录组关联研究以探索基因与其与RA风险的关联之间的关系。
RA与中风之间存在全基因组显著的正相关（遗传相关性 = 0.3756）。在局部基因组区域中，chr2:201572564-202,829,668区域内RA与中风之间的相关性最为显著（p = 0.0015）。我们鉴定出179个显著的SNP以及RA和中风的五个共同风险基因（IRF5、RNASET2、ZNF438、UBE2LS和SYNGR1）。这些基因参与免疫炎症途径。
研究结果表明RA与中风之间存在共同的遗传结构。这些发现可能为RA和中风的发病机制提供新的见解，并有助于开发新的诊断标志物和治疗靶向药物，以改善RA和中风患者的临床结局。
