ArticleDiabetes care2026
Clinical Utility of a Type 1 Diabetes Genetic Risk Score Measured as Part of MODY Genetic Testing.
Article in Diabetes care, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveTo evaluate the clinical utility of incorporating a type 1 diabetes genetic risk score (T1DGRS) into monogenic diabetes gene panel testing for individuals referred for suspected maturity-onset diabetes of the young (MODY) from routine clinical practice. RESEARCH DESIGN AND
methodsWe studied 1,129 individuals treated with insulin referred for MODY genetic testing. All underwent gene panel testing that included 10 variants to calculate T1DGRS. We compared T1DGRS distributions with reference populations to estimate the type 1 diabetes (T1D) prevalence within referred individuals. We defined age-specific T1DGRS thresholds to identify probable T1D (positive predictive value ≥80%) and applied them in individuals genetically unsolved MODY to assess its utility as a pregenetic testing triage tool.
resultsT1DGRS in MODY referral individuals was intermediate between reference populations with and without T1D, consistent with an estimated 20% (95% CI 14.9-25.2%) T1D in this real-world setting. After genetic testing, no excess T1DGRS was observed in individuals with genetically solved MODY, whereas those with unsolved MODY showed enrichment consistent with 26.0% T1D, with highest values in children (76.2%) and lowest in adults (16.8%). Age-specific T1DGRS thresholds identified 16.1% (95% CI 13.8-18.5%) of genetically unsolved MODY as probable T1D. As a pretesting tool, T1DGRS showed limited discrimination overall (area under the curve [AUC] 0.60) but performed well in children aged <10 years (AUC 0.83), where >50% of tests could be avoided without missing MODY.
conclusionsIncorporating a T1DGRS into routine MODY gene panel testing is feasible and clinically valuable. This approach broadens genomic diagnostics beyond monogenic disease by identifying T1D in individuals with genetically unsolved MODY. Pregenetic testing utility is age dependent and may reduce unnecessary testing in pediatric patients.
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