Lipid metabolism and osteonecrosis: unraveling causal mechanisms via multi-omics and mendelian randomization.

ABSTRACT: Osteonecrosis (ON), a debilitating condition marked by ischemic bone death, has been clinically linked to dysregulated lipid metabolism, yet the causal relationships and underlying genetic mechanisms remain poorly defined. This study employed bidirectional Mendelian randomization (MR) analyses using genome-wide association study (GWAS) datasets to investigate causal effects between 179 plasma lipid species and ON. Functional enrichment and protein-protein interaction (PPI) analyses were conducted to identify key genes, followed by transcriptomic validation using public datasets and experimental confirmation through qRT-PCR and immunohistochemistry. MR analysis revealed that four lipid species had protective effects against ON, while two were associated with increased risk. Conversely, ON i

SUBMITTER: Chen Y 

PROVIDER: S-EPMC12589827 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature