ArticleDiabetes2025
Diabetes Genetic Clusters and Clinical Outcomes in American Indians.
Kaylia M Reynolds, Quan Sun, Ying Zhang, Jason Umans, Shelley A Cole, Andrew P Morris, Nora Franceschini
Abstract read
In one paragraphArticle in Diabetes, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
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5 · Who and what moneyAuthors and funding
7 authors.
Kaylia M ReynoldsDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.
Quan SunDepartment of Biostatistics, University of North Carolina, Chapel Hill, NC.
Ying ZhangThe University of Oklahoma Health Sciences, Oklahoma City, OK.
Jason UmansMedStar Institute, Washington, DC.
Shelley A ColeTexas Biomedical Research Institute, San Antonio, TX.
Andrew P MorrisCentre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, U.K.ORCID 0000-0002-6805-6014 Nora FranceschiniDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.ORCID 0000-0001-9755-2175 Funding
The Southwest National Primate Research Center Supplement- Infrastructure improvements of ABSL2 holding areasP51OD011133 · OD · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI Larry S. Schlesinger · 2012 to 2026
$129.7MThe Strong Heart Study, Phase VU01HL041654 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI LEE, ELISA TAN · 1988 to 2013
$19.2MSTRONG HEART STUDY (SHS): OUHSC COORDINATING CENTER - TASK AREA B (B.1 AND B.3)75N92019D00027 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ZHANG, YING · 2019 to 2025
$15.5MCARDIOVASCULAR DISEASE IN THE PIMA INDIANSU01HL041642 · NHLBI · MEDSTAR RESEARCH INSTITUTE · PI HOWARD, BARBARA V · 1988 to 2013
$12.6MSTRONG HEART FAMILY STUDYU01HL065520 · NHLBI · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI COLE, SHELLEY A · 2000 to 2011
$8.9MCARDIOVASCULAR DISEASE IN SIOUX INDIANSU01HL041652 · NHLBI · U.S. PHS INDIAN HEALTH SERVICE · PI BEST, LYLE G · 1988 to 2013
$7.9MSTRONG HEART STUDY (SHS)-MISSOURI BREAKS INDUSTRIES RESEARCH, INC.- FIELD CENTER (FC) TASK AREA B (B.1 AND B.3)75N92019D00029 · NHLBI · MISSOURI BREAKS RESEARCH, INC. · PI FRETTS, AMANDA MAE · 2019 to 2025
$7.5MSTRONG HEART STUDY (SHS)- UNIVERSITY OF OKLAHOMA-FIELD CENTER (FC), TASK AREA B.3, YEAR 375N92019D00028 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ALI, TAUQEER · 2019 to 2025
$6.5MSTRONG HEART STUDY (SHS)- MEDSTAR HEALTH RESEARCH INSTITUTE (MHRI) FIELD CENTER -SUBTASK AREA B.2 PHASE VII EXAM AND EXAM CLOSEOUT.75N92019D00030 · NHLBI · MEDSTAR HEALTH RESEARCH INSTITUTE · PI UMANS, JASON G · 2019 to 2025
$5.2MCVD in American Indians Study and Data Management Center and OK Field CenterR01HL109284 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI STONER, JULIE A · 2013 to 2018
$4.6MCARDIOVASCULAR EVALUATION--STRONG HEART STUDY PHASE IVU01HL065521 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI DEVEREUX, RICHARD B · 2000 to 2013
$4.3MLeveraging ancestry to map kidney lociR01MD012765 · NIMHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FRANCESCHINI, NORA · 2017 to 2021
$3.6MIndian Health Service (IHS)NHLBI NIH HHS 75N92019D00027NHLBI NIH HHS 75N92019D00028NHLBI NIH HHS 75N92019D00029NHLBI NIH HHS 75N92019D00030NHLBI NIH HHS R01 HL109282NHLBI NIH HHS R01 HL109284NHLBI NIH HHS R01 HL109301NHLBI NIH HHS R01 HL109315NHLBI NIH HHS R01 HL109319NHLBI NIH HHS R01 HL163972NHLBI NIH HHS R01HL163972NHLBI NIH HHS R01 HL175681NHLBI NIH HHS U01 HL041642NHLBI NIH HHS U01 HL041652NHLBI NIH HHS U01 HL041654NHLBI NIH HHS U01 HL065520NHLBI NIH HHS U01 HL065521NIDDK NIH HHS K26 DK138425NIDDK NIH HHS R01 DK117445NIDDK NIH HHS R01DK117445NIH HHS P51 OD011133NIHR Manchester Biomedical Research Centre 21754NIHR Manchester Biomedical Research Centre NIHR203308NIMHD NIH HHS R01 MD012765the National Institute on Minority Health and Health Disparities, NIH R01MD012765the NHLBI, NIH, Department of Health and Human Services R01HL109282the NHLBI, NIH, Department of Health and Human Services R01HL109284the NHLBI, NIH, Department of Health and Human Services R01HL109301the NHLBI, NIH, Department of Health and Human Services R01HL109315the NHLBI, NIH, Department of Health and Human Services R01HL109319the NHLBI, NIH, Department of Health and Human Services U01HL41642the NHLBI, NIH, Department of Health and Human Services U01HL41652the NHLBI, NIH, Department of Health and Human Services U01HL41654the NHLBI, NIH, Department of Health and Human Services U01HL65520the NHLBI, NIH, Department of Health and Human Services U01HL65521
6 · The paper itselfAbstract
Diabetes has a large medical and public health impact in American Indians. Studies have used genetic data to distinguish type 1 diabetes (T1D) and type 2 diabetes (T2D) and uncover biologic mechanisms underlying T2D clinical heterogeneity. We applied a T1D polygenic score (PS) to 3,084 American Indians (mean age 56 years, 58% women, 39% diabetes). We also calculated partitioned PS for eight clusters of T2D-associated variants and evaluated their association with 20 cardiometabolic traits and five clinical outcomes. The profile of T1D PS for individuals with diabetes was consistent with T2D. A total T2D PS was significantly associated with early age of T2D onset (P = 3.5 × 10-11). Partitioned PS for T2D clusters were significantly associated with cardiometabolic traits for the obesity cluster (increased measures of body fat and total triglycerides but lower HDL cholesterol), while the lipodystrophy cluster was associated with increased fasting insulin, waist-to-hip ratio, triglycerides, and blood pressure, and lower body fat percentage and HDL cholesterol. T2D clusters were not associated with cardiovascular and kidney outcomes. Our findings support a relationship of cluster-specific T2D partitioned PS with cardiometabolic traits described in other populations, but there are opportunities for developing improved clustering methods using genetic variation from American Indians. ARTICLE HIGHLIGHTS: Diabetes is highly prevalent in American Indians and a main cause of morbidity and mortality, and its clinical heterogeneity can be uncovered using genetic data. We are interested in identifying type 1 versus type 2 diabetes in American Indians with diabetes and identifying biological mechanisms for type 2 diabetes that are related to clinical outcomes using genetic data. Using genetic data, we found a high probability of participants having type 2 diabetes. We identified similar associations of type 2 diabetes genetic clusters, that are related to biological mechanisms, with cardiometabolic traits as previously described in other populations, but no associations of genetic clusters with cardiovascular and kidney outcomes. Our findings support type 2 diabetes as the main cause of diabetes in our American Indian cohort and provide insights into improvements using genetic data to uncover type 2 biological mechanisms.
Indexed as
American Indian or Alaska NativeDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2AdultAgedFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedMultifactorial Inheritance
Identifiers
PMID40824997
PMCPMC12585164
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