Genetic risk score distinguishes type 1 diabetes in Spanish study

Researchers assessed genetic risk scores for type 1 diabetes (T1D) differential diagnosis and risk stratification in a Spanish population. Of 2,338 genotyped individuals, 2,215 passed quality control: 816 with T1D, 469 with type 2 diabetes, 457 with monogenic diabetes, and 473 controls. The observational study compared a newly developed Spanish-specific score with HLA-DRB1 and two established European-derived scores, and examined associations with age at T1D onset.

T1D-GRS2 distinguished T1D from controls better than the Spanish-specific score, with ROC areas under the curve of 0.888 (95% CI 0.867–0.908) versus 0.837 (0.797–0.877; p=0.001). Discrimination against type 2 and monogenic diabetes remained high, at 0.886 (0.865–0.907). In the combined pediatric-onset T1D and control cohort, the P50 cutoff provided 80% sensitivity and 81% specificity. The P25 cutoff increased sensitivity to 97%, while P75 increased specificity to 96%. Higher scores were associated with childhood rather than adulthood onset, primarily driven by HLA.

These findings support genetic risk scoring as a complementary aid to diabetes classification, rather than a standalone diagnostic test. The population was restricted to Spanish participants of European ancestry, limiting generalizability. Only the abstract was available; prospective screening performance and benefits of score-guided intervention were not reported.