Kreienkamp Raymond J, Deutsch Aaron J, Huerta-Chagoya Alicia, Borglund Erin M, Florez Jose C, Flannick Jason, Udler Miriam S
Division of Endocrinology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Center for Genomic Medicine and Diabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Horm Res Paediatr. 2025 May 20:1-9. doi: 10.1159/000546445.
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.
对于医疗服务提供者而言，准确分类小儿糖尿病可能具有挑战性，而错误分类可能导致护理效果欠佳。近年来，1型糖尿病（T1D）多基因评分已被开发出来，它基于T1D风险等位基因负担来量化个体患T1D的遗传风险，在区分T1D和非T1D方面具有良好的辨别能力。如果在临床中使用，这些工具有可能显著提高诊断的准确性。
我们将T1D多基因评分应用于波士顿儿童医院精准链接生物样本库中一组有基因数据的小儿患者（n = 1846），其中包括96名被诊断为T1D的个体。
与对照组相比，临床诊断为T1D的患者T1D多基因评分更高（Wilcoxon秩和检验p < 0.0001）。在74名患有糖尿病且T1D多基因评分超过区分T1D与非T1D的外部验证临界值的个体中，有69人被确诊为T1D。有多个案例显示T1D多基因评分具有临床实用性。T1D多基因评分升高提示一名胰腺自身抗体（PAA）阴性、青年成年型糖尿病（MODY）基因检测阴性且表型符合T1D的个体患有T1D。T1D多基因评分较低准确地表明一名被发现患有HNF1B-MODY的个体患有非典型糖尿病。一名个体PAA呈阳性，但医疗服务提供者指出该患者可能没有典型的T1D，后来较低的T1D多基因评分也证实了这一点。
T1D多基因评分已具有临床实用性，有助于准确诊断小儿糖尿病。现在需要努力推动其在临床实践中的应用。
