Transcriptome regulation analysis in osteoarthritis primary tissues identifies high-confidence effector genes
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Osteoarthritis, a whole-joint degenerative disorder, is a major public health burden that affects nearly 600 million individuals worldwide. Molecular profiling of relevant tissues is crucial for understanding the biological mechanisms underlying disease development. We present the first comprehensive map of transcriptional regulation of disease-relevant primary tissues from knee osteoarthritis patients: macroscopically intact (low-grade, N=263) and degenerated (high-grade, N=216) cartilage, synovium (N=278), and fat pad (N=94). Of 9,738 unique expression quantitative trait loci (eQTL)-associated genes, 60.6% have not been reported previously. We identify 51 genes with directional evidence of tissue-specific colocalization and causal association with knee osteoarthritis, 25 of which are new high-confidence effector genes for osteoarthritis (including MUSTN1 , which is implicated in cartilage integrity). Our study provides valuable insights into the tissue-specific and shared molecular mechanisms underlying osteoarthritis and offers drug repurposing opportunities.
