The utility of a type 2 diabetes polygenic score in addition to clinical variables for prediction of type 2 diabetes incidence in birth, youth and adult cohorts in an Indigenous study population
Authors' conclusion
This study demonstrates that a European-derived PS contributes significantly to prediction of type 2 diabetes incidence in addition to information provided by clinical variables in this Indigenous study population. Discriminatory power of the PS was similar to that of other commonly measured clinical variables (e.g. HbA1c). Including type 2 diabetes PS in addition to clinical variables may be clinically beneficial for identifying individuals at higher risk for the disease, especially at younger ages.
Study context
- Population
- Indigenous population from the Southwestern USA with high T2D prevalence, without diabetes at baseline; adult cohort (2333, from age ≥20 years, 640 cases), youth cohort (2229, age 5–19 years, 228 cases), birth cohort (2894, from birth, 438 cases)three cohorts
- Comparison
- Clinical variables plus T2D polygenic score vs clinical variables alone
- Outcome
- Prediction of incident T2D
Methodological detailsthree cohorts: adult, youth, birth, ten PS constructions compared
- Three cohorts: adult, youth, birth
- Ten PS constructions compared
Performance
As reported in the abstract
Prediction of incident T2D (AUC; PS HR per SD)
- Adult cohort AUC: clinical variables vs with PS
- 0.728 vs 0.735
- Adult cohort PS HR per SD
- 1.27 (95% CI 1.17, 1.38; p=1.6 × 10-8)
- Youth cohort AUC: clinical variables vs with PS
- 0.805 vs 0.812
- Youth cohort PS HR
- 1.49 (95% CI 1.29, 1.72; p=4.3 × 10-8)
- Birth cohort AUC: clinical variables vs with PS
- 0.614 vs 0.685
- Birth cohort PS HR
- 1.48 (95% CI 1.35, 1.63; p=2.8 × 10-16)
Further findings
Net reclassification improvement (NRI)
- NRI for PS, adult cohort
- 0.270
- NRI for PS, youth cohort
- 0.268
- NRI for PS, birth cohort
- 0.362
- NRI for HbA1c, adult cohort
- 0.267
- NRI for HbA1c, youth cohort
- 0.173
Decision curve analysis
- Net benefit of adding PS to clinical variables most pronounced at moderately stringent threshold probabilities for a preventive intervention, across all cohorts
Original publication
The utility of a type 2 diabetes polygenic score in addition to clinical variables for prediction of type 2 diabetes incidence in birth, youth and adult cohorts in an Indigenous study population. Diabetologia. Published 2 March 2023. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →