Type 1 Diabetes Genetic Risk Score: A Novel Tool to Discriminate Monogenic and Type 1 Diabetes

Area of Science:

• Genetics
• Endocrinology
• Diabetes Research

Background:

• Differentiating monogenic diabetes from type 1 diabetes (T1D) is crucial for appropriate clinical management and genetic research.
• Current diagnostic methods may not always clearly distinguish between these diabetes subtypes.

Purpose of the Study:

• To evaluate the utility of a type 1 diabetes genetic risk score (T1D-GRS) in discriminating monogenic diabetes from T1D.
• To assess the T1D-GRS's effectiveness in identifying patients with neonatal diabetes (NDM) of monogenic origin.

Main Methods:

• Developed a T1D-GRS using common genetic variants associated with T1D.
• Applied the T1D-GRS to cohorts of patients with maturity-onset diabetes of the young (MODY), T1D, and neonatal diabetes (NDM).
• Utilized receiver operating characteristic (ROC) analysis to determine the discriminative power of the T1D-GRS.

Main Results:

• The T1D-GRS demonstrated high accuracy (AUC = 0.87) in distinguishing MODY and T1D.
• A T1D-GRS above the 50th T1D centile strongly indicated T1D (94% specificity).
• In NDM patients, lower T1D-GRS values correlated with confirmed monogenic causes, while higher values suggested potential novel monogenic etiologies or T1D.

Conclusions:

• The T1D-GRS is a novel and effective tool for differentiating monogenic diabetes from T1D.
• This genetic risk score can improve diagnostic accuracy and patient stratification in diabetes care.
• The T1D-GRS aids in identifying individuals with potential novel monogenic diabetes forms, particularly within the NDM population.