Department of Orthopaedics of the First Affiliated Hospital, Medical School, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
J Orthop Surg Res. 2023 Sep 4;18(1):659. doi: 10.1186/s13018-023-04029-4.
Spondyloarthritis (SpA) is a group of multifactorial bone diseases influenced by genetic factors, the environment and lifestyle. However, current studies have found a limited number of SpA-related genes, and the genetic and pathogenic mechanisms of SpA are still unclear.
A tissue-specific transcriptome-wide association study (TWAS) of SpA was performed using GWAS (including 3966 SpA patients and 448,298 controls) summary data and gene expression weights of whole blood and skeletal muscle. The SpA-associated genes identified by TWAS were further compared with the differentially expressed genes (DEGs) identified in the SpA gene expression profile acquired from the Gene Expression Omnibus database (GEO, GSE58667). Finally, functional enrichment and annotation analyses of the identified genes were performed.
The TWAS detected 499 suggestive genes associated with SpA in whole blood and skeletal muscle, such as CTNNAL1 (P = 3.04 × 10, P = 9.58 × 10). The gene expression profile of SpA identified 20 candidate genes that overlapped in the TWAS data, such as MCM4 (P = 1.32 × 10, P = 2.75 × 10) and KIAA1109 (P = 3.71 × 10, P = 4.67 × 10). Enrichment analysis of the genes identified by TWAS identified 93 significant GO terms and 33 KEGG pathways, such as mitochondrion organization (GO: 0007005) and axon guidance (hsa04360).
We identified multiple candidate genes that were genetically related to SpA. Our study may provide novel clues regarding the genetic mechanism, diagnosis, and treatment of SpA.
脊柱关节炎（SpA）是一组受遗传因素、环境和生活方式影响的多因素骨病。然而，目前的研究发现与 SpA 相关的基因数量有限，SpA 的遗传和发病机制仍不清楚。
使用全血和骨骼肌的 GWAS（包括 3966 例 SpA 患者和 448298 例对照）汇总数据和基因表达权重，进行 SpA 的组织特异性全基因组关联研究（TWAS）。通过 TWAS 鉴定的与 SpA 相关的基因，与从基因表达综合数据库（GEO，GSE58667）获得的 SpA 基因表达谱中鉴定的差异表达基因（DEG）进行比较。最后，对鉴定的基因进行功能富集和注释分析。
TWAS 在全血和骨骼肌中检测到 499 个与 SpA 相关的提示基因，如 CTNNAL1（P=3.04×10，P=9.58×10）。SpA 的基因表达谱鉴定出 20 个与 TWAS 数据重叠的候选基因，如 MCM4（P=1.32×10，P=2.75×10）和 KIAA1109（P=3.71×10，P=4.67×10）。TWAS 鉴定基因的富集分析确定了 93 个显著的 GO 术语和 33 个 KEGG 途径，如线粒体组织（GO：0007005）和轴突导向（hsa04360）。
我们鉴定了多个与 SpA 遗传相关的候选基因。我们的研究可能为 SpA 的遗传机制、诊断和治疗提供新的线索。
