A Large-Scale Multi-omics Polygenic Risk Score Analysis Identified Candidate Biomarkers Associated with Heel Bone Mineral Density - PubMed
3 hours ago
- #Multi-omics
- #Osteoporosis
- #Bone Mineral Density
- A large-scale multi-omics polygenic risk score (PRS) analysis identified candidate biomarkers associated with heel bone mineral density (hBMD).
- The study utilized QTLs data from the INTERVAL cohort and calculated PRS for RNAs, proteins, and metabolites in the UK Biobank (UKB).
- hBMD was measured via quantitative ultrasound, and associations were evaluated in 96,165 subjects using a generalized linear model.
- 195 hBMD-associated genes (e.g., WNT16), 180 proteins (e.g., COL1A1), and 21 metabolites (e.g., total cholesterol) were identified.
- Replication analysis confirmed associations for proteins like COL1A1 and metabolites like total cholesterol in UKB data.
- Integrated multi-omics analysis highlighted pathways like glycerophospholipid metabolism, involving genes/metabolites such as DGKZ, PLPP3, and glycerol 3-phosphate.
- Mendelian randomization (MR) identified causal biomarkers for hBMD, including NAP1L2 and PLPP3.
- Novel candidate biomarkers (e.g., PLPP3, RGMB, RNF128) were identified, providing genetic evidence for their role in bone mineral regulation.
- The findings offer insights into the molecular mechanisms of osteoporosis (OP).