{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:35:28Z","timestamp":1793111728126,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"publisher","award":["CPP2021-008725"],"award-info":[{"award-number":["CPP2021-008725"]}],"id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"ERDF","doi-asserted-by":"publisher","award":["PRE-2023-2-0084_MOD:A"],"award-info":[{"award-number":["PRE-2023-2-0084_MOD:A"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Accurate type 1 diabetes (T1D) risk assessment can improve diagnosis and preventive care, reducing misdiagnosis and enabling preclinical interventions. Genetic risk scores (GRS) offer a promising tool, but population-specific validation is required.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to assess the performance of established scores vs a novel Spanish-specific GRS for T1D differential diagnosis and risk stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>From 2338 genotyped individuals, 2215 Spanish participants of European ancestry passed quality control: 816 T1D, 469 type 2 diabetes (T2D), 457 monogenic diabetes (MD), and 473 controls. A novel Spanish-specific GRS (T1D-SP-GRS) was developed and compared with HLA-DRB1 and 2 European-derived models (T1D-GRS and T1D-GRS2). The best-performing score was evaluated for T1D discrimination vs T2D and MD and for association with T1D-onset age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>T1D-GRS2 outperformed T1D-SP-GRS for T1D vs controls (AUC-ROC: 0.888 [95% CI: 0.867-0.908] vs 0.837 [0.797-0.877], P = .001), retaining high discrimination vs T2D and MD (0.886 [0.865-0.907]). In the combined pediatric-onset T1D and control cohort, the P50 cutoff yielded a sensitivity of 0.80 (95% CI: 0.76-0.84) and specificity of 0.81 (0.77-0.84); P25 prioritized sensitivity (0.97 [0.95-0.99]) while P75 specificity (0.96 [0.93-0.97]). A P90 threshold conferred 26-fold higher T1D odds vs controls and 18- and 17-fold vs T2D and MD (P &amp;lt; .001). Higher T1D-GRS2 in childhood- vs adulthood-onset T1D revealed an age-dependent risk profile primarily driven by HLA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>T1D-GRS2 discriminates T1D from other diabetes etiologies, providing a complementary tool to support diagnostic accuracy. The higher genetic risk associated with a younger age at onset provides key insights for early-stage T1D screening and intervention strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag188","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:36:29Z","timestamp":1791891389000},"page":"635-645","source":"Crossref","is-referenced-by-count":0,"title":["A genetic risk approach to differential diagnosis of type 1 diabetes and risk stratification in the Spanish population"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5112-552X","authenticated-orcid":false,"given":"Laura","family":"Saso-Jim\u00e9nez","sequence":"first","affiliation":[{"name":"Genetics and Control of Diabetes and Other Endocrine Disorders, Biobizkaia Health Research Institute , Barakaldo 48903 ,","place":["Spain"]},{"name":"Faculty of Medicine and Nursing, University of the Basque Country (UPV\/EHU) , Leioa 48940 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