Type 1 Diabetes Polygenic Scores Improve Diagnostic Accuracy in Pediatric Diabetes Care

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.

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.

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.

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.