{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T19:05:48Z","timestamp":1784574348244,"version":"3.55.0"},"reference-count":43,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["UM1DK078616"],"award-info":[{"award-number":["UM1DK078616"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Large-scale multiancestry genome-wide association studies have identified hundreds of loci associated with type 2 diabetes (T2D) and glycemic traits, yet imputed genotyping arrays limit the detection of low-frequency and rare variants. Whole-genome sequencing (WGS) offers a more complete view of genetic variation, especially across diverse populations. We analyzed high-coverage (38\u00d7) WGS data from 21,913 T2D case subjects, 61,036 control subjects, and up to 50,011 individuals with no diabetes with fasting glucose, fasting insulin, and HbA1c from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine Program. We performed single-variant association testing, conditional analysis, fine-mapping, and Bayesian colocalization to identify genetic signals and assess regulatory relevance in diabetes-related tissues. We identified 76 distinct association signals across 34 loci, including novel variants at DUSP9 for T2D, and ROBO1, NDN, and MYT1 for HbA1c. Fine-mapping narrowed credible sets and improved causal variant resolution. Colocalization highlighted 80 expression signals in diabetes-related tissues, linking genetic associations to functional regulatory mechanisms. Our findings demonstrate the utility of WGS to uncover novel variants in diverse populations, enhance locus resolution, and link regulatory variation to disease-relevant tissues. This work refines the genetic architecture of T2D and glycemic traits and supports precision medicine efforts targeting diverse populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>We aimed to improve understanding of the genetic architecture of type 2 diabetes and glycemic traits by leveraging whole-genome sequencing in diverse populations. Our goal was to identify novel variants, refine known loci, and link genetic signals to regulatory mechanisms through colocalization with expression quantitative trait loci. We discovered novel variants, significantly improved fine-mapping resolution, and identified 80 regulatory colocalization signals in diabetes-relevant tissues. These findings support precision medicine approaches by connecting genetic variation to functional biology in type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0557","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T13:50:01Z","timestamp":1781185801000},"page":"1477-1491","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Colocalization of eQTLs With Type 2 Diabetes and Glycemic Traits Using Whole-Genome Sequences in Diverse Populations From the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program"],"prefix":"10.2337","volume":"75","author":[{"given":"Ningyuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biostatistics, Boston University School of Public Health 1 , Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Barnard","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic 5 , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Blangero","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine 6 , Brownsville, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald W.","family":"Bowden","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Wake Forest University of Medicine 7 , Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-6756","authenticated-orcid":false,"given":"April P.","family":"Carson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Mississippi Medical Center 8 , Jackson, MS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yii-Der Ida","family":"Chen","sequence":"additional","affiliation":[{"name":"The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center 9 , Torrance, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Heart, Vascular & Thoracic Institute; Cardiovascular and Metabolic Sciences, Lerner Research Institute 10 , Cleveland Clinic, Cleveland, OH"},{"name":"Cleveland Clinic Lerner College of Medicine, Case Western Reserve University 11 , Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne E.","family":"Curran","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and 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