Multi-omics approach unveils novel therapeutic targets for osteoporosis: integrated analysis of Asian and European gene-tissue expression consortium data

• Identified 64 genes significantly associated with osteoporosis via SMR analysis, with HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, and HLA-DRB5 validated across Asian and European cohorts. • Colocalization analysis provided evidence for HLA-DQA2 and HLA-DQB1, and plasma HLA-DQA2 levels were inversely associated with osteoporosis risk. • Single-cell analysis revealed increased abundance of dendritic cells, B cells, macrophages, and neutrophils in the osteoporotic immune microenvironment. • Enrichment analysis highlighted the MHC class II antigen presentation pathway as a key mechanism, suggesting novel therapeutic targets for osteoporosis.