Discrepancy Between Genetically Predicted and Observed BMI Predicts Incident Type 2 Diabetes
Main finding · Incident T2D, adjusted for observed BMIResult — go to the resultAdjusted hazard ratio 1.61 95% CI 1.26–2.05Authors' conclusion
Having a higher BMI than genetically predicted is associated with an increased risk of T2D. These findings underscore the potential to reassess T2D risk based on individual levels of obesity using genetic thresholds for BMI.
Study context
- Population
- UK Biobank participants of European ancestry without T2D; replication in Korean Genome and Epidemiology Study (KoGES) cohort, South Koreatest set n = 115,119 · South Korea 7,430
- Participants
- 332,154 participants
- Exposure
- Quintiles of BMI-diff
- Outcome
- Incident T2D
- Follow-up
- 10 years
Methodological detailsUK Biobank, polygenic risk score (PRS-CS), multivariable Cox proportional hazards model, train and test sets, external replication in KoGES
- UK Biobank
- Polygenic risk score (PRS-CS)
- Multivariable Cox proportional hazards model
- Train and test sets
- External replication in KoGES
Main finding
Incident T2D, adjusted for observed BMI · 10-year follow-up
Adjusted hazard ratio
1.61
95% CI 1.26–2.05
P < 0.001
1st quintilevs 5th quintile
aHR 1.61 (95% CI 1.26–2.05); P < 0.001
As reported in the abstract
Observational data: associations, not effects.
Further findings
Variance of BMI explained by genetically predicted BMI (test set)
- Variance of BMI explained
- 7.1%
T2D cases in test set · 10-year follow-up
- T2D cases
- 3,599 (3.1%)
Replication in KoGES
- Results were consistent in KoGES
Insulin sensitivity
- Higher BMI than predicted associated with impaired insulin sensitivity
Original publication
Discrepancy Between Genetically Predicted and Observed BMI Predicts Incident Type 2 Diabetes. Diabetes Care. Published 13 August 2024. doi:10.
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