Femoral neck width genetic risk score is a novel independent risk factor for hip fractures
Authors' conclusion
We conclude that the underlying biology regulating FNW and FN-BMD differs, and that DXA-derived FNW is causally related to hip fractures independently of FN-BMD, adding information beyond FN-BMD for hip fracture prediction.
Study context
- Population
- UK Biobank participants; Femoral neck width (FNW) genome-wide association study (GWAS) on hip DXA scans of 38,150 individuals (mean age 63.8 yr, 48.0% males); GRS analysis in UK Biobank (UKB) excluding the GWAS populationFNW GWAS population
- Participants
- 38,150 participants
- Comparison
- Genetically determined FNW vs femoral neck bone mineral density (FN-BMD) in relation to hip fracture risk
- Outcome
- Hip fracture risk (all hip, femoral neck, trochanteric) in relation to FNW independently of FN-BMD
Methodological detailsGWAS, genetic risk score analysis, Cox proportional hazards model
- GWAS
- Genetic risk score analysis
- Cox proportional hazards model
Performance
As reported in the abstract
Genetically determined FNW (Mendelian randomization), per SD increase
All hip fractures, OR (95% CI) per SD increase in FNW
1.53
1.29–1.82
Femoral neck fractures, OR per SD increase in FNW
1.58
1.30–1.92
Further findings
FNW GWAS
- Independent genome-wide significant FNW SNPs (genes for cartilage differentiation, hedgehog, skeletal development; FN-BMD SNPs mainly runx1/Wnt signaling)
- 71
Incident hip fracture by GRS (Cox model)
- FNW GRS, all incident hip fractures, HR
- 1.08 (1.05-1.12)
- FNW GRS, femoral neck fractures, HR
- 1.10 (1.06-1.15)
- FNW GRS not associated with trochanteric fractures
- FN-BMD GRS associated with reduced risk of all hip fracture types
- n = 338 742, 3222 cases; FNW GWAS population excluded
Original publication
Femoral neck width genetic risk score is a novel independent risk factor for hip fractures. J Bone Miner Res. Published 12 January 2024. doi:10.
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