biostudies-literatureYu GFood and Health BureauResearch Grants Council, University Grants CommitteeChinese University of Hong KongCroucher Foundation602-614https://www.ebi.ac.uk/biostudies/studies/S-EPMC11832604biostudies-literatureUnknown68(3)<h4>Aims/hypothesis</h4>Type 2 diabetes is a complex and heterogeneous disease and the aetiological components underlying the heterogeneity remain unclear in the Chinese and East Asian population. Therefore, we aimed to investigate whether specific pathophysiological pathways drive the clinical heterogeneity in type 2 diabetes.<h4>Methods</h4>We employed newly developed type 2 diabetes hard-clustering and soft-clustering pathway-specific polygenic risk scores (psPRSs) to characterise individual genetic susceptibility to pathophysiological pathways implicated in type 2 diabetes in 18,217 Chinese patients from Hong Kong. The 'total' type 2 diabetes polygenic risk score (PRS) was summed by genome-wide significant type 2 diabetes signals (n=1289). We examined the associations between psPRSs anDiabetologiaType 2 diabetes pathway-specific polygenic risk scores elucidate heterogeneity in clinical presentation, disease progression and diabetic complications in 18,217 Chinese individuals with type 2 diabetes.PMC11832604Research Committee Postdoctoral Fellowship SchemeCroucher Foundation Senior Medical Research FellowDirect GrantHealthInternationalisation Faculty Mobility SchemeResearch Impact Fund (CU R4012-18)Theme-based Research Scheme (T12-402/13N)University Grants Matching SchemeMedical Research Fund (CFS-CUHK2)Provost's Scheme for PhD scholarship of the ChinFocused Innovation SchemeOzaki RHuang CSo WYShi MYu GHong Kong Diabetes Biobank Study GroupFung SHou YTam CHTSiu SCWu HSzeto CCKam GChow ETam WHMa RCWLee HMTsang CCCheng YLLau ESHKong APSFan BTsang MWChan JCNOram RALuk AOYYeung VTFLee KFTRANSCEND ConsortiumCheung HMYang ACheung EYNLim CKPHui GLeung JYYLi JKYLo SWeedon MNLau ITLau KPLau ENg ACWfalseType 2 diabetes pathway-specific polygenic risk scores elucidate heterogeneity in clinical presentation, disease progression and diabetic complications in 18,217 Chinese individuals with type 2 diabetes.<h4>Aims/hypothesis</h4>Type 2 diabetes is a complex and heterogeneous disease and the aetiological components underlying the heterogeneity remain unclear in the Chinese and East Asian population. Therefore, we aimed to investigate whether specific pathophysiological pathways drive the clinical heterogeneity in type 2 diabetes.<h4>Methods</h4>We employed newly developed type 2 diabetes hard-clustering and soft-clustering pathway-specific polygenic risk scores (psPRSs) to characterise individual genetic susceptibility to pathophysiological pathways implicated in type 2 diabetes in 18,217 Chinese patients from Hong Kong. The 'total' type 2 diabetes polygenic risk score (PRS) was summed by genome-wide significant type 2 diabetes signals (n=1289). We examined the associations between psPRSs an2025-01-01T00:00:00Z2025 Mar2025-04-18T12:59:49.742Z2025-04-04T02:00:57.487ZS-EPMC118326043953104110.1007/s00125-024-06309-y