{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:02:16Z","timestamp":1780459336856,"version":"3.54.1"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100028802","name":"Society of Transnational Academic Researchers Scholars Network","doi-asserted-by":"publisher","award":["STAR21109"],"award-info":[{"award-number":["STAR21109"]}],"id":[{"id":"10.13039\/100028802","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100028802","name":"Society of Transnational Academic Researchers Scholars Network","doi-asserted-by":"publisher","award":["STAR22206"],"award-info":[{"award-number":["STAR22206"]}],"id":[{"id":"10.13039\/100028802","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Risk of cardiorenal complications varies among patients with type 2 diabetes (T2D). T2D pathway\u2010specific polygenic risk scores (psPRS) capture genetic susceptibility related to distinct intermediate biological processes associated with T2D and cardiorenal outcomes, predominantly in European populations. Their relevance in multi\u2010ethnic Asian populations remains unclear. We explored associations between T2D\u2010derived psPRS and cardiorenal outcomes and circulating proteins linked to cardiorenal complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 2057 multi\u2010ethnic individuals with T2D from the prospective SMART2D cohort. Eight T2D pathway\u2010related psPRS (Beta\u2010cell +Proinsulin [PI], Beta\u2010cell \u2212PI, residual glycaemia, body fat, metabolic syndrome, obesity, lipodystrophy, liver and lipid metabolism) were constructed using East Asian\u2010specific effect sizes. Cox regression was used to assess associations with incident end\u2010stage kidney disease (ESKD) and heart failure (HF), logistic regression for rapid decline in kidney function (RDKF) and linear regression for circulating proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The Beta\u2010cell \u2212PI psPRS was inversely associated with ESKD (HR\u2009=\u20090.81; 95% CI: 0.69\u20130.95), RDKF (OR\u2009=\u20090.81; 95% CI: 0.69\u20130.94) and HF (HR\u2009=\u20090.86; 95% CI: 0.74\u20131.00). In contrast, the lipodystrophy psPRS was associated with higher odds of RDKF (OR\u2009=\u20091.21; 95% CI: 1.04\u20131.41). The Beta\u2010cell \u2212PI psPRS was also associated with circulating levels of LILRA5, EDA2R and FABP4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In a multi\u2010ethnic Asian population, pathway\u2010specific genetic susceptibility was differentially associated with cardiorenal outcomes and related circulating proteins. These findings suggest the potential relevance of biologically informed genetic pathways in diverse populations and warrant validation in independent cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70741","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T11:17:06Z","timestamp":1775647026000},"page":"5330-5338","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathway\u2010Specific Polygenic Risk Scores and Cardiorenal Complications in Asians With Type 2 Diabetes"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8772-4452","authenticated-orcid":false,"given":"Resham L.","family":"Gurung","sequence":"first","affiliation":[{"name":"Clinical Research Unit Khoo Teck Puat Hospital  Singapore Singapore"},{"name":"Cardiovascular and Metabolic Disorders Signature Research Program Duke\u2010NUS Medical School  Singapore 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