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

Objective: Genetic risk scores (GRS) 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 GRS 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 GRS 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.