Figure 5.

The OA-critical cell populations in bulk RNA-seq data and GWAS associations. (A) The heatmap shows cell compositions of 18 healthy controls and 20 patients with OA from GSE114007. The values in brackets represent the Spearman’s correlation (r) between patients with OA and non-OA controls. FC and preHTC are highly correlated with OA status. (B) The bar plot depicts the fraction of chondrocytes that are related to OA, where Scissor+ denotes the positively correlated (pink), Scissor− is negatively correlated (green), and the others are uncorrelated chondrocytes (grey). The top three populations, ProC, FC and preHTC are positively correlated with OA status. (C) The heatmap illustrates the two subtypes of 131 OA samples identified by hierarchical cluster with ward.D2 parameter. 131 samples are clustered into 2 subtypes: group A (n=43): an inflammation-related subtype with less fraction of preFCs and group B (n= 88): a non-inflammatory-related subtype with more fraction of preFCs. (D) The volcano plot shows the differentially expressed genes between group A versus group B. (E) The significant Gene Ontology terms were enriched by the upregulated/downregulated DE genes. The upregulated DE genes in group A (inflammation-related subtype) were mainly involved in inflammatory and immune response-associated pathways, while group B (non-inflammatory-related subtype) upregulated DE genes were mainly involved in chondrocyte proliferation pathways. (F) The scatter plot shows the correlation between the cell population contribution to OA as determined from GWAS of individuals with Asian ancestry (n=1979) and the corresponding contribution derived from GWAS of individuals with European ancestry (n=406 241). HTC population is significantly associated with OA in individuals with European ancestry and has the smallest p value with East Asian ancestry. GWAS, genome-wide association studies; InfC, inflammatory chondrocyte; OA, osteoarthritis; preFC, prefibrocartilage chondrocyte; preHTC, prehypertrophic chondrocyte.