Introduction: Accurately classifying pediatric diabetes can be challenging for providers, and misclassification can result in suboptimal care. In recent years, type 1 diabetes (T1D) polygenic scores, which quantify one's genetic risk for T1D based on T1D risk allele burden, have been developed with good discriminating capacity between T1D and not-T1D. These tools have the potential to improve significantly diagnostic provider accuracy if used in clinic.
Methods: We applied T1D polygenic scores to a group of pediatric patients (n = 1,846) with genetic data available in the Boston Children's Hospital PrecisionLink Biobank, including 96 individuals diagnosed with T1D.
Results: Patients with a clinical diagnosis of T1D had higher T1D polygenic scores compared to controls (Wilcoxon rank-sum p < 0.0001). Sixty-nine of the 74 individuals with diabetes and a T1D polygenic score exceeding an externally validated cutoff for distinguishing T1D from not-T1D were confirmed to have T1D. There were multiple cases where T1D polygenic scores would have clinical utility. An elevated T1D polygenic score suggested T1D in a pancreatic autoantibody (PAA)-negative individual with negative maturity-onset diabetes of the young (MODY) genetic testing and a phenotype matching T1D. A low T1D polygenic score accurately indicated atypical diabetes in an individual found to have HNF1B-MODY. One individual had positive PAA, but the provider noted that the patient may not have classic T1D, as later suggested by a low T1D polygenic score.
Conclusion: T1D polygenic scores already have clinical utility to aid in the accurate diagnosis of pediatric diabetes. Efforts are now needed to advance their use in clinical practice.
Keywords: Genetics; Pediatric diabetes; Polygenic scores.
© 2025 S. Karger AG, Basel.