{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:14:34Z","timestamp":1788412474433,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"publisher","award":["NPRP11C\u20100115\u2010180010"],"award-info":[{"award-number":["NPRP11C\u20100115\u2010180010"]}],"id":[{"id":"10.13039\/100008982","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":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Type 2 diabetes (T2D) is a complex and highly heterogeneous disease driven in part by genetic predisposition and can be stratified into clinical subgroups to aid disease management. We recently grouped T2D subjects in the Qatar Biobank (QBB) cohort into Severe Insulin\u2010Deficient Diabetes (SIDD), Severe Insulin\u2010Resistant Diabetes (SIRD), Mild Obesity\u2010Related Diabetes (MOD) and Mild Age\u2010Related Diabetes (MARD) subtypes. Herein, we focused on the genetic makeup of these subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used the QBB cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913,808), of whom 2687 were with T2D, and comprehensively assessed polygenic risk scores (PGS) across T2D subtypes, investigated genetic loci associated with each subtype by leveraging the most recent and largest GWAS for T2D, evaluated SNP associations across T2D genetic clusters, and identified protein interaction pathways associated with these distinct T2D subtypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MOD showed consistently lower PGS compared with other T2D subtypes across all tested scores. SIDD showed more associations with SNPs mapping to residual glycemic cluster compared with other T2D subtypes. The incremental analysis of PGS004838 demonstrated a high \u0394AUC of 0.101 for SIDD and a moderate \u0394AUC of 0.068 for SIRD, but not for MOD and MARD. Protein interaction analyses identified candidate subtype\u2010associated gene networks linked to pathways related to glucose homeostasis in SIDD, insulin signalling and hepatic metabolism in SIRD, body fat distribution in MOD and vascular\u2010related processes in MARD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We found heterogeneous genetic architectures across clinically defined T2D subtypes in a Middle Eastern population. Our findings provide evidence supporting differential polygenic burden, subtype genetic associations and subtype\u2010associated biological pathways across T2D subtypes. These observations support the utility of subtype\u2010based genetic analyses for improving biological understanding of T2D heterogeneity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71159","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T03:40:58Z","timestamp":1785469258000},"page":"9450-9460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Refining the Genetic Contribution to Type 2 Diabetes Subtypes"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8717-0309","authenticated-orcid":false,"given":"Nayra M.","family":"Al\u2010Thani","sequence":"first","affiliation":[{"name":"College of Health and Life Sciences (CHLS) Hamad Bin Khalifa University (HBKU)  Doha Qatar"},{"name":"Bioinformatics Core Weill Cornell Medicine\u2010Qatar, Education City  Doha Qatar"},{"name":"Diabetes Research Centre (DRC), Qatar Biomedical Research Institute (QBRI) Hamad Bin Khalifa University (HBKU)  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman M.","family":"Toor","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences (CHLS) Hamad Bin Khalifa University (HBKU)  Doha Qatar"},{"name":"Diabetes Research Centre (DRC), Qatar Biomedical Research Institute (QBRI) Hamad Bin Khalifa University (HBKU)  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umm\u2010Kulthum Ismail","family":"Umlai","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences (CHLS) Hamad Bin Khalifa University (HBKU)  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9716-5332","authenticated-orcid":false,"given":"Usama","family":"Aliyu","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences (CHLS) Hamad Bin Khalifa University (HBKU)  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Suhre","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Weill Cornell Medicine\u2010Qatar, Education City  Doha Qatar"},{"name":"Englander Institute for Precision Medicine Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5916-5983","authenticated-orcid":false,"given":"Omar M. 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