Genetic risk and polygenic risk score assessment of prediabetes and progression to type 2 diabetes
Authors' conclusion
This study identified two genetic loci associated with prediabetes. PGS004838 showed the highest performance in predicting prediabetes and progression to T2D, with the strongest effect reported to date. Our findings have clinical translation potential in risk stratification and early intervention.
Study context
- Population
- Qatar Biobank (QBB) participants; follow-up cohort of individuals without diabetes at baselinefollow-up cohort n = 2143
- Participants
- 10,932 participants
- Comparison
- Prediabetes vs normoglycaemia; 140 existing PGS for T2D
- Prediabetesn = 2,267
- Normoglycaemian = 8,665reference
- Outcome
- Susceptibility loci to prediabetes; performance of existing PGS for T2D in predicting prevalent prediabetes and progression to diabetes
Methodological detailscase-control Genome-Wide Association Study (GWAS), logistic regression (baseline cohort), Cox regression (follow-up cohort)
- Case-control GWAS
- Logistic regression (baseline cohort)
- Cox regression (follow-up cohort)
Performance
As reported in the abstract
GWAS loci associated with prediabetes (p < 5 × 10-8), near GCK and HK1
2
PGS004838 association with prediabetes, OR/SD
1.37
95% CI 1.29–1.45p-value: 4.45 × 10-27
Further findings
Progression to T2D · 6.0 years median follow-up
- Progressed to T2D among 2143 without diabetes at baseline
- 9.3%
- PGS004838 HR/SD for progression to T2D
- 1.79 (95% CI 1.53-2.10; p-value: 2.08 × 10-13)
- Very high vs intermediate genetic risk quintile: increased risk of progressing to T2D (very high quintile younger)
- 2.4-fold
- PGS004838 outperformed the other 139 PGS
Original publication
Genetic risk and polygenic risk score assessment of prediabetes and progression to type 2 diabetes. Diabetes Obes Metab. Published 5 June 2025. doi:10.
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