基于大规模跨疾病全基因组关联研究鉴定与三种自身免疫性疾病相关的类风湿关节炎共享遗传位点和共同风险基因。
Identifying shared genetic loci and common risk genes of rheumatoid arthritis associated with three autoimmune diseases based on large-scale cross-trait genome-wide association studies.
机构信息
National Center for Applied Mathematics in Hunan, Xiangtan University, Hunan, China.
Key Laboratory of Intelligent Computing and Information Processing of Ministry of Education, Xiangtan University, Hunan, China.
出版信息
Front Immunol. 2023 Jun 12;14:1160397. doi: 10.3389/fimmu.2023.1160397. eCollection 2023.
INTRODUCTION
Substantial links between autoimmune diseases have been shown by an increasing number of studies, and one hypothesis for this comorbidity is that there is a common genetic cause.
METHODS
In this paper, a large-scale cross-trait Genome-wide Association Studies (GWAS) was conducted to investigate the genetic overlap among rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and type 1 diabetes.
RESULTS AND DISCUSSION
Through the local genetic correlation analysis, 2 regions with locally significant genetic associations between rheumatoid arthritis and multiple sclerosis, and 4 regions with locally significant genetic associations between rheumatoid arthritis and type 1 diabetes were discovered. By cross-trait meta-analysis, 58 independent loci associated with rheumatoid arthritis and multiple sclerosis, 86 independent loci associated with rheumatoid arthritis and inflammatory bowel disease, and 107 independent loci associated with rheumatoid arthritis and type 1 diabetes were identified with genome-wide significance. In addition, 82 common risk genes were found through genetic identification. Based on gene set enrichment analysis, it was found that shared genes are enriched in exposed dermal system, calf, musculoskeletal, subcutaneous fat, thyroid and other tissues, and are also significantly enriched in 35 biological pathways. To verify the association between diseases, Mendelian randomized analysis was performed, which shows possible causal associations between rheumatoid arthritis and multiple sclerosis, and between rheumatoid arthritis and type 1 diabetes. The common genetic structure of rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and type 1 diabetes was explored by these studies, and it is believed that this important discovery will lead to new ideas for clinical treatment.
简介
越来越多的研究表明自身免疫性疾病之间存在着实质性的联系，而这种共病的一个假设是存在共同的遗传原因。
方法
在本文中，进行了大规模的跨疾病全基因组关联研究（GWAS），以研究类风湿关节炎、多发性硬化症、炎症性肠病和 1 型糖尿病之间的遗传重叠。
结果与讨论
通过局部遗传相关分析，发现了类风湿关节炎与多发性硬化症之间存在局部显著遗传关联的 2 个区域，以及类风湿关节炎与 1 型糖尿病之间存在局部显著遗传关联的 4 个区域。通过跨疾病荟萃分析，确定了 58 个与类风湿关节炎和多发性硬化症相关的独立位点、86 个与类风湿关节炎和炎症性肠病相关的独立位点以及 107 个与类风湿关节炎和 1 型糖尿病相关的独立位点，这些都达到了全基因组显著水平。此外，还通过遗传鉴定发现了 82 个共同的风险基因。基于基因集富集分析，发现共享基因富集在暴露的皮肤系统、小腿、肌肉骨骼、皮下脂肪、甲状腺和其他组织中，并且在 35 个生物学途径中也显著富集。为了验证疾病之间的关联，进行了孟德尔随机分析，结果表明类风湿关节炎和多发性硬化症之间以及类风湿关节炎和 1 型糖尿病之间可能存在因果关联。通过这些研究探索了类风湿关节炎、多发性硬化症、炎症性肠病和 1 型糖尿病的共同遗传结构，相信这一重要发现将为临床治疗带来新的思路。
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