OBJECTIVE

The goal of this study was 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-reported on the personal family history health questionnaire. A PRS was constructed from 1,289 variants identified from a large multiancestry genome-wide association study meta-analysis for T2D. Logistic regression models were run to generate odds ratios (ORs) and 95% CIs for T2D. All models were adjusted for age, sex, and BMI.

RESULTS

A total of 109,958 AoU research participants were included in the analysis. The odds of T2D increased with 1 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 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, although the ORs were slightly attenuated. Predictive models that included both the PRS and family history (area under the curve [AUC] 0.794) performed better than models including only family history (AUC 0.763) or the PRS (AUC 0.785).

CONCLUSIONS

In predicting T2D, inclusion of a T2D PRS in addition to family history of T2D (first-degree relatives) added statistical value. Further study is needed to determine whether consideration of both family history and a PRS would be useful for clinical T2D prediction.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

This article contains supplementary material online at https://doi.org/10.2337/figshare.27694530.

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