Single-Cell Integration of BMD GWAS Results Prioritize Candidate Genes Influencing Age-Related Bone Loss.

ABSTRACT: The regulation of bone mineral density (BMD) is highly influenced by genetics and age. Although genome-wide association studies (GWAS) for BMD have uncovered many genes through their proximity to associated variants (variant nearest-neighbor [VNN] genes), the cell-specific mechanisms of each VNN gene remain unclear. This is primarily due to the inability to prioritize these genes by cell type and age-related expression. Using age-related transcriptomics, we found that the expression of many VNN genes was upregulated in the bone and marrow from aged mice. Candidate genes from GWAS were investigated using single-cell RNA-sequencing (scRNA-seq) datasets to enrich for cell-specific expression signatures. VNN candidate genes are highly enriched in osteo-lineage cells, osteocytes, hypertrophic c

SUBMITTER: Doolittle ML 

PROVIDER: S-EPMC10556272 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature