Genetically Proxied GIP ‐ GIPR Pathway Perturbation and Fracture Risk
Main finding · Fractures at major osteoporotic sites (GIP-GIPR perturbation, scaled to 1 kg/m² lower BMI)Result — go to the resultOdds ratio 0.80 95% CI 0.66–0.98Authors' conclusion
Human genetic evidence suggests an association between genetically proxied GIP-GIPR pathway perturbation and lower fracture risk
Study context
- Population
- Unrelated UK Biobank participants
- Participants
- 401,983 participants
- Comparison
- Genetically proxied GIP-GIPR (and GCG-GLP1R) pathway perturbation vs genome-wide liability to lower BMI or HbA1c
- Outcome
- Fractures at major osteoporotic sites
Methodological detailscis genetic variants, UK Biobank
- Cis genetic variants
- UK Biobank
Main finding
As reported in the abstract
Fractures at major osteoporotic sites (GIP-GIPR perturbation, scaled to 1 kg/m² lower BMI)
Odds ratio
0.80
95% CI 0.66–0.98
GIP-GIPR perturbation
OR 0.80 (95% CI 0.66–0.98)
Further findings
Combined spine-and-hip fractures
- Associations similar for combined spine-and-hip fractures under both scaling approaches (lower BMI or HbA1c), OR
- 0.68, 0.49-0.94 (95% CI)
Genome-wide liability to lower BMI or HbA1c
- Genome-wide liability to lower BMI or HbA1c did not show the same fracture associations as GIP-GIPR perturbation
GCG-GLP1R perturbation and fractures
- GCG-GLP1R estimates were imprecise
Estimated bone mineral density (eBMD)
- Genetically proxied incretin pathway perturbation was not associated with eBMD
Time to fracture (Cox), per SD of GIP-GIPR genetic risk score
- Fractures at major osteoporotic sites, HR
- 0.976, 0.959-0.992 (95% CI)
- Combined spine-and-hip fractures, HR
- 0.971, 0.946-0.996 (95% CI)
Original publication
Genetically Proxied GIP ‐ GIPR Pathway Perturbation and Fracture Risk. Diabetes Obes Metab. Published 29 September 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →