20.500.12556/DiRROS-24610 Polygenic score from MODY genes is associated with type 1 diabetes and disease characteristics Aims: This study evaluates the contribution of common variants in Maturity-Onset Diabetes of the Young (MODY) genes on type 1 diabetes (T1D), using a polygenic score (PGS) approach. Methods: 485 children and youth diagnosed with T1D from at least 1 year and 271 healthy controls (HC) were recruited. Personal information (i.e. age, sex, height, weight) were collected for each participant, and clinical information (i.e. age at diagnosis, disease duration, presence of autoantibodies and ketoacidosis at onset (DKA)) were also obtained for T1D subjects. Participants were genotyped using Illumina Infinium Global Screening Array. PGS based on Single Nucleotide Polymorphisms (SNPs) in 16 MODY genes were developed. The association of this PGS with T1D susceptibility and clinical disease characteristics was assessed by regression analysis. Results: A PGS including 335 SNPs in MODY genes discriminates T1D from HC (AUC = 60.1%, AIC = 787.6). This PGS was significantly higher in T1D compared to HC (p-value = 0.0004, pseudo-R2 = 2.85%). Moreover, regression analysis between PGS and T1D clinical characteristics showed higher PGS values in T1D subjects with zinc transporter 8 autoantibodies (ZnT8A) compared with T1D subjects without ZnT8A (p-value = 0.04). A similar trend was also observed for antibodies directed against glutamic acid decarboxylase (GADA), although the association did not reach statistical significance (p-value = 0.06). Conclusions: Our study suggests that a polygenic approach based on MODY genes may discriminate T1D from HC and may contribute to patient stratification, helping to better understand T1D heterogeneity. type 1 diabetes MODY polygenic score autoantibody true false true Angleški jezik Ni določen Neznano 2025-12-09 11:03:32 2025-12-09 11:03:33 2025-12-10 03:45:40 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis vira z dne 30. 9. 2025; str. 2021-2029 Vol. 62 2025 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 616.379 1432-5233 10.1007/s00592-025-02544-w 250987523 RAZ_Catamo_Eulalia_2025.pdf RAZ_Catamo_Eulalia_2025.pdf 1 302D706E2B3F6334F135084121DA15A2 9bb641b76c4da84b33b54258a156699ae9a8c38d06f621cf378475814f40bfbd 7569369c-d4e6-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36718 https://link.springer.com/article/10.1007/s00592-025-02544-w 0 84525856-d4e6-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36719 Univerzitetni klinični center Ljubljana 0 0 0