Validation of GenProb-T1D and its clinical utility for differentiating types of diabetes in a biobank from a US healthcare system.

Atypical diabetes with overlapping clinical features of type 1 (T1D) and type 2 (T2D) is common and challenging diagnostically and for implementing effective treatment. Here, we validate a recently reported genetic probability of type 1 diabetes (GenProb-T1D) from the UK Biobank (UKB) for differentiating type 1 diabetes and type 2 diabetes in a diabetes patient cohort from a healthcare system-based biobank in the USA. Among 3,363 diabetes patients, we confirmed the performance of GenProb-T1D in differentiating typical type 1 diabetes vs type 2 diabetes. Furthermore, for 359 atypical diabetes patients, those with GenProb-T1D higher than the pre-defined cutoff derived from the UKB had clinical presentations more consistent with that of typical type 1 diabetes. Similar findings were found in participants of European and non-European ancestries. This study provides necessary validation to translate GenProb-T1D into genetic testing in a multi-ancestry cohort. Measuring underlying genetic susceptibility of type 1 diabetes and type 2 diabetes can supplement current clinical tools for earlier and more accurate diagnoses of diabetes.