biostudies-literatureSiddiqui MKNational Institute for Health Research (NIHR)Wellcome Trust396https://www.ebi.ac.uk/biostudies/studies/S-EPMC12460670biostudies-literatureUnknown5(1)<h4>Background</h4>Individuals of South and East Asian ancestry have a higher risk of type 2 diabetes, often driven by insulin deficiency due to impaired beta-cell function. The transcription factor XBP1 supports beta-cell survival by reducing cellular stress, but its role in diabetes risk and glucose regulation remains unclear. This study aimed to evaluate the impact of XBP1 expression on diabetes risk, beta-cell function, glycaemic traits, and treatment response across ancestries.<h4>Methods</h4>We performed colocalisation analyses to test whether XBP1 expression in pancreatic islets and type 2 diabetes share causal variants. A lead variant regulating XBP1 expression was identified and analysed in two South Asian cohorts from India to assess associations with beta-cell function and glucoCommunications medicineXBP1 expression in pancreatic islet cells is associated with poor glycaemic control especially in young non-obese onset diabetes across ancestries.PMC1246067016/136/10099177/Z/12/ZCollier DPalmer CNAChaudhary SHodgson SZengeya IMcNeilly ADurham CVinuela ADowlut SMartin HGenes & Health Research TeamSiddiqui MKAkhtar SHussain SWinckley CMohan VMantle EIyer VWright JTaylor ASartori AMacArthur DDupuis TVenkatesan RAsif ATrembath RCEto FJan WhalleyBreen GWalter KRussell JSpreckley MMazid MBAnjana RMHarvey JColligan GStow DHurles MKalantzis GDavtian DCantley JIslam KRison SPopov ISafa NPradeepa RDawed AYGafton JAngel AHunt KABidi SSalman AQureshi AZollner JMason DSattar NBigossi MDeloukas PNewman BSolly JFiner SHeng TPearson ERBrown AASrinivasan SSaravanan JAdedire ETOwor ETricker KOvchinnikov VChung RLee SHMaher EKhan AYasmin SMorton CVan Heel DALangenberg CMathur RKhatun HGriffiths CAshraf SJacobs BMSamuel MSimpson MAsgar OfalseXBP1 expression in pancreatic islet cells is associated with poor glycaemic control especially in young non-obese onset diabetes across ancestries.<h4>Background</h4>Individuals of South and East Asian ancestry have a higher risk of type 2 diabetes, often driven by insulin deficiency due to impaired beta-cell function. The transcription factor XBP1 supports beta-cell survival by reducing cellular stress, but its role in diabetes risk and glucose regulation remains unclear. This study aimed to evaluate the impact of XBP1 expression on diabetes risk, beta-cell function, glycaemic traits, and treatment response across ancestries.<h4>Methods</h4>We performed colocalisation analyses to test whether XBP1 expression in pancreatic islets and type 2 diabetes share causal variants. A lead variant regulating XBP1 expression was identified and analysed in two South Asian cohorts from India to assess associations with beta-cell function and gluco2025-01-01T00:00:00Z2025 Sep2026-07-15T06:45:39.765Z2026-06-30T03:22:38.669ZS-EPMC124606704099328510.1038/s43856-025-01076-2