Additive value of polygenic risk score to family history for type 2 diabetes prediction: Results from the All of US Research Database
Objective: The goal of this study is to assess the additive value of considering type 2 diabetes (T2D) polygenic risk score (PRS) in addition to family history for T2D prediction.
Research Design and Methods: Data were obtained from the All of Us (AoU) research database. First degree T2D family history was self-report from the personal family history health questionnaire. A PRS was constructed from 1,289 variants identified from a large multi-ancestry GWAS meta-analysis for T2D. Logistic regression models were run to generate odds ratios (OR) and 95% confidence intervals (95% CI) for T2D. All models were adjusted for age, sex, and body mass index (BMI).
Results: A total of 109,958 AoU research participants were included in the analysis. The odds for T2D increased with 1 standard deviation (SD) PRS (OR: 1.75, 95% CI 1.71-1.79) and positive T2D family history (OR: 2.32, 95% CI 2.20-2.43). In the joint model, both the 1 SD PRS (OR: 1.69, 95% CI 1.65-1.72) and family history (OR: 2.06, 95% CI 1.98-2.15) were significantly associated with T2D, though the OR were slightly attenuated. Predictive models that included both PRS and family history (AUC=0.794) performed better than models including family history (AUC=0.763) or PRS (AUC=0.785).
Conclusions: In predicting T2D, inclusion of a T2D PRS in addition to family history of T2D (first degree relatives) has added statistical value. Further study is needed to determine whether consideration of both family history and PRS would be useful for clinical T2D prediction.