Genomic structural equation modeling reveals the shared genetic architecture of osteosarcopenia across five musculoskeletal phenotypes - PubMed
2 hours ago
- #genomic-sem
- #shared-genetics
- #osteosarcopenia
- Genomic structural equation modeling identified shared genetic architecture across five musculoskeletal phenotypes related to osteosarcopenia.
- A single-factor model captured shared genetic liability, with handgrip strength and appendicular lean mass loading most strongly.
- The study identified 58,696 genome-wide significant SNPs and 29 novel loci, with fine-mapping prioritizing 317 high-confidence causal variants.
- Key genes identified include BMP6, ACAN, IHH, LRP5, SOX5, IGF1R, FOXO3, and IRS1.
- Pathway analysis revealed enrichment in endochondral ossification and growth hormone/insulin-like growth factor-1 signaling.
- Cell-type enrichment localized risk to mesenchymal stem cells and skeletal muscle satellite cells, with spatial mapping highlighting cartilage primordium.