Integrating transcriptome-wide study and mRNA expression profiles yields novel insights into the biological mechanism of chondropathies

BACKGROUND: Chondropathies are a group of cartilage diseases, which share some common pathogenetic features. The etiology of chondropathies is still largely obscure now. METHODS: A transcriptome-wide association study (TWAS) was performed using the UK Biobank genome-wide association study (GWAS) data of chondropathies (including 1314 chondropathy patients and 450,950 controls) with gene expression references of muscle skeleton (MS) and peripheral blood (YBL). The candidate genes identified by TWAS were further compared with three gene expression profiles of osteoarthritis (OA), cartilage tumor (CT), and spinal disc herniation (SDH), to confirm the functional relevance between the chondropathies and the candidate genes identified by TWAS. Functional mapping and annotation (FUMA) was used for the gene ontology enrichment analyses. Immunohistochemistry (IHC) was conducted to validate the accuracy of integrative analysis results. RESULTS: Integrating TWAS and mRNA expression profiles detected 84 candidate genes for knee OA, such as DDX20 (P(TWAS YBL) = 1.79 × 10(− 3), fold change (FC) = 2.69), 10 candidate genes for CT, such as SRGN (P(TWAS YBL) = 1.46 × 10(− 3), FC = 3.36), and 4 candidate genes for SDH, such as SUPV3L1 (P(TWAS YBL) = 3.59 × 10(− 3), FC = 3.22). Gene set enrichment analysis detected 73 GO terms for knee OA, 3 GO terms for CT, and 1 GO term for SDH, such as mitochondrial protein complex (P = 7.31 × 10(− 5)) for knee OA, cytokine for CT (P = 1.13 × 10(− 4)), and ion binding for SDH (P = 3.55 × 10(− 4)). IHC confirmed that the protein expression level of DDX20 was significantly different between knee OA cartilage and healthy control cartilage (P = 0.0358). CONCLUSIONS: Multiple candidate genes and GO terms were detected for chondropathies. Our findings may provide a novel insight in the molecular mechanisms of chondropathies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-019-1978-8) contains supplementary material, which is available to authorized users.