Utility of type 1 diabetes genetic risk score in a non-European population: insights from an Iranian cohort

Abstract Background The present study aimed to investigate the efficiency of the type 1 diabetes genetic risk score (T1D GRS) in distinguishing between patients with type 1 and type 2 diabetes in Iran, an underrepresented population in genomic research. Methods We included 13,318 participants in the Tehran-Cardiometabolic Genetic Study (TCGS) cohort, classified into individuals without diabetes, with pre-diabetes, with type 2 diabetes, and with type 1 diabetes. Two T1D GRSs and one T2D GRS were calculated and compared between groups using the Wilcoxon test. The ability of genetic risk scores to discriminate T1D and T2D was assessed using the pROC package. Results Both T1D GRSs displayed significantly higher scores in the T1D group than in other groups. Notably, T1D GRS2 effectively distinguished T1D from T2D in individuals diagnosed before age 40 (AUC = 0.8, P = 5.8e-7). This performance was even stronger for those under age 25 at diagnosis (AUC = 0.88, P = 3.2e-6). Additionally, we observed a higher median of the T1D GRS2 z-score within the T1D group and the T2D GRS z-score within the T2D group, further supporting the specificity of the tested GRSs in the Iranian population. Conclusion Our findings suggest that T1D GRS2, particularly in younger patients, shows promise for improved T1D diagnosis and potentially newborn screening in this population. This could facilitate equitable access to precision medicine approaches for individuals in the area.