Transcriptome-wide association study identifies new susceptibility genes and pathways for spondyloarthritis

BACKGROUND: 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. METHODS: 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. RESULTS: The TWAS detected 499 suggestive genes associated with SpA in whole blood and skeletal muscle, such as CTNNAL1 (P(SM) = 3.04 × 10(−2), P(WB) = 9.58 × 10(−3)). The gene expression profile of SpA identified 20 candidate genes that overlapped in the TWAS data, such as MCM4 (P(TWAS) = 1.32 × 10(−2), P(DEG) = 2.75 × 10(−2)) and KIAA1109 (P(TWAS) = 3.71 × 10(−2), P(DEG) = 4.67 × 10(−2)). 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). CONCLUSION: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13018-023-04029-4.