The clinical utility of the bone mineral density (BMD)-related comprehensive genome-wide polygenic score in identifying individuals with a high risk of osteoporotic fractures
Authors' conclusion
Our findings suggested that an efficient PGS estimate enables the identification of strata with up to a 1.7-fold difference in fracture incidence.
Study context
- Population
- European ancestry individuals from the UK Biobank
- Participants
- 455,663 individuals
- Exposure
- Genome-wide polygenic score (PGSs) for femoral neck and total body BMD, alone and combined with clinical risk factors, vs previously published restricted PGS and FRAX base model
- Outcome
- Incident (osteoporotic) fracture
Methodological detailsgenome-wide polygenic score development and external validation, reclassification analysis vs FRAX base model
- Genome-wide polygenic score development and external validation
- Reclassification analysis vs FRAX base model
Main finding
As reported in the abstract
Incident fracture per unit decrease in PGS
Weakest of four PGSs (formula not shown), HR
1.03
95% CI 1.01–1.05p = 0.001
Strongest of four PGSs (formula not shown), HR
1.17
95% CI 1.15–1.19p < 0.0001
Observational data: associations, not effects.
Further findings
Reclassification of fracture vs FRAX base model (reclassification analysis)
- Improvement in reclassification of fracture with each of the four PGS models added, respectively, vs FRAX base model
- 1.2% (95% CI, 1.0 to 1.3%), 0.2% (95% CI, 0.1 to 0.3%), 1.4% (95% CI, 1.3 to 1.5%), and 2.2% (95% CI, 2.1 to 2.4%)
- The PGSs are given as formulas in the abstract, not by name
Original publication
The clinical utility of the BMD-related comprehensive genome-wide polygenic score in identifying individuals with a high risk of osteoporotic fractures. Osteoporos Int. Published 9 January 2023. doi:10.
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