Genetic variants of glucose-dependent insulinotropic polypeptide (GIP) signalling as proxy for body weight reduction and cardiovascular risk
Authors' conclusion
Genetic proxies for body weight reduction via GIP receptor targeting reduces the risk of MACE and heart failure, mediated partly through lower BMI and partly through lower HbA1c.
Study context
- Population
- UK Biobank participants (one-sample Mendelian randomization (MR)); FinnGen summary statistics (two-sample MR)FinnGen n = 419,821
- Participants
- 408,056 participants
- Exposure
- Genetically proxied body mass index (BMI) reduction via GIP/GIPR score vs polygenic BMI score
- Outcome
- MACE and HF risk per 1 kg/m² lower BMI
Methodological detailsone-sample MR, two-sample MR, observational analyses
- One-sample MR
- Two-sample MR
- Observational analyses
Main finding
As reported in the abstract
Risk per 1 kg/m² lower BMI (one-sample MR)
| Group | Major adverse cardiovascular events (MACE) | HF |
|---|---|---|
| GIP/GIPR score | 29% lower risk (P = .0002) | 43% lower risk (P = 5 × 10⁻⁵) |
| Polygenic BMI score | 3% lower risk (P = .002) | 13% lower risk (P < 1 × 10-300) |
Major adverse cardiovascular events (MACE)
GIP/GIPR score29% lower risk (P = .0002)
Polygenic BMI score3% lower risk (P = .002)
HF
GIP/GIPR score43% lower risk (P = 5 × 10⁻⁵)
Polygenic BMI score13% lower risk (P < 1 × 10-300)
Observational data: associations, not effects.
Further findings
Two-sample MR (FinnGen)
- Similar results
Mediation of GIP/GIPR score effect by BMI and HbA1c
- MACE: mediated by BMI
- 13%
- MACE: mediated by HbA1c
- 22%
- HF: mediated by BMI
- 16%
- HF: mediated by HbA1c
- 17%
- All P ≤ 7 × 10-5
Original publication
Genetic variants of glucose-dependent insulinotropic polypeptide (GIP) signalling as proxy for body weight reduction and cardiovascular risk. Eur Heart J. Published 7 October 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →