Utility of Diabetes Type-Specific Genetic Risk Scores for the Classification of Diabetes Type Among Multiethnic Youth

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Oram, R. A.
Sharp, S. A.
Pihoker, C.
Ferrat, L.
Imperatore, G.
Williams, A.
Redondo, M. J.
Wagenknecht, L.
Dolan, L. M.
Lawrence, J. M.
Diabetes care
Journal Article
American Diabetes Association
© 2022 by the American Diabetes Association.
OBJECTIVE: Genetic risk scores (GRSs) aid classification of diabetes type in White European adult populations. We aimed to assess the utility of GRS in the classification of diabetes type among racially/ethnically diverse youth in the U.S. RESEARCH DESIGN AND METHODS: We generated type 1 diabetes (T1D)- and type 2 diabetes (T2D)-specific GRSs in 2,045 individuals from the SEARCH for Diabetes in Youth study. We assessed the distribution of genetic risk stratified by diabetes autoantibody positive or negative (DAA+/-) and insulin sensitivity (IS) or insulin resistance (IR) and self-reported race/ethnicity (White, Black, Hispanic, and other). RESULTS: T1D and T2D GRSs were strong independent predictors of etiologic type. The T1D GRS was highest in the DAA+/IS group and lowest in the DAA-/IR group, with the inverse relationship observed with the T2D GRS. Discrimination was similar across all racial/ethnic groups but showed differences in score distribution. Clustering by combined genetic risk showed DAA+/IR and DAA-/IS individuals had a greater probability of T1D than T2D. In DAA- individuals, genetic probability of T1D identified individuals most likely to progress to absolute insulin deficiency. CONCLUSIONS: Diabetes type-specific GRS are consistent predictors of diabetes type across racial/ethnic groups in a U.S. youth cohort, but future work needs to account for differences in GRS distribution by ancestry. T1D and T2D GRS may have particular utility for classification of DAA- children.
Diabetes Care. 2022 Mar 21:dc202872. doi: 10.2337/dc20-2872.
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