biostudies-literatureThomas NJNIDDK NIH HHSMedical Research CouncilDiabetes UKNational Institute for Health Research (NIHR)Wellcome Trust2258-2265https://www.ebi.ac.uk/biostudies/studies/S-EPMC8423681biostudies-literatureUnknown64(10)<h4>Aims/hypothesis</h4>Among white European children developing type 1 diabetes, the otherwise common HLA haplotype DR15-DQ6 is rare, and highly protective. Adult-onset type 1 diabetes is now known to represent more overall cases than childhood onset, but it is not known whether DR15-DQ6 is protective in older-adult-onset type 1 diabetes. We sought to quantify DR15-DQ6 protection against type 1 diabetes as age of onset increased.<h4>Methods</h4>In two independent cohorts we assessed the proportion of type 1 diabetes cases presenting through the first 50 years of life with DR15-DQ6, compared with population controls. In the After Diabetes Diagnosis Research Support System-2 (ADDRESS-2) cohort (n = 1458) clinician-diagnosed type 1 diabetes was confirmed by positivity for one or more islet-sDiabetologiaDR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life.PMC8423681MC_PC_1722817/0005757220601/Z/20/Z219606/Z/19/Z16/0005529MC_QA137853U01 DK127382WT097835MFPatel KAHagopian WAOliver NSWeedon MNThomas NJJohnston DGDennis JMWalkey HCSharp SAKaur AOram RAMisra SfalseDR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life.<h4>Aims/hypothesis</h4>Among white European children developing type 1 diabetes, the otherwise common HLA haplotype DR15-DQ6 is rare, and highly protective. Adult-onset type 1 diabetes is now known to represent more overall cases than childhood onset, but it is not known whether DR15-DQ6 is protective in older-adult-onset type 1 diabetes. We sought to quantify DR15-DQ6 protection against type 1 diabetes as age of onset increased.<h4>Methods</h4>In two independent cohorts we assessed the proportion of type 1 diabetes cases presenting through the first 50 years of life with DR15-DQ6, compared with population controls. In the After Diabetes Diagnosis Research Support System-2 (ADDRESS-2) cohort (n = 1458) clinician-diagnosed type 1 diabetes was confirmed by positivity for one or more islet-s2021-01-01T00:00:00Z2021 Oct2026-05-09T07:19:00.033Z2022-02-11T12:29:34.645ZS-EPMC84236813427258010.1007/s00125-021-05513-4