ArticleDiabetes care2022
Type 2 Diabetes Partitioned Polygenic Scores Associate With Disease Outcomes in 454,193 Individuals Across 13 Cohorts.
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Article in Diabetes care, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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44 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Dissecting Schizophrenia Biology Using Pleiotropy With Cognitive Genomics.Biological psychiatry · 2025Pooled it
- Increased Genetic Risk for β-Cell Failure Is Associated With β-Cell Function Decline in People With Prediabetes.Diabetes · 2024Trial
- Polygenic risk scores and plasma proteomics identify cancer-related proteins and trans-regulated protein networks.Cell genomics · 2026Article
- Converging TCF7L2 and CDKAL1 pathways in the pathogenesis of type 2 diabetes mellitus.Acta diabetologica · 2026Review
- Heterogeneous endocrine cell composition defines human islet functional phenotypes.Nature communications · 2026Article
- Mapping disease loci to biological processes via joint pleiotropic and epigenomic partitioning.Cell genomics · 2026Article
- Diabetogenic processes for insulin resistance-linked hyperinsulinaemia are associated with colorectal cancer.Diabetologia · 2026Article
- Genetic Predictors of Response to Oral Insulin for Type 1 Diabetes Prevention.Diabetes care · 2026Article
- Diabetes Genetic Clusters and Clinical Outcomes in the Chronic Renal Insufficiency Cohort.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- Multi-molecular scores map process-specific polygenic diabetes risk to atherosclerosis, cardiometabolic diseases, and vascular complications.medRxiv : the preprint server for health sciences · 2026Article
- Opportunistic screening of type 2 diabetes with deep metric learning using electronic health records.Scientific reports · 2025Article
- Leveraging and partitioning polygenic risk scores to identify cancer-related proteins.medRxiv : the preprint server for health sciences · 2025Article
- Heterogeneity in the development of diabetes-related complications: narrative review of the roles of ancestry and geographical determinants.Diabetologia · 2025Review
- From omics to AI-mapping the pathogenic pathways in type 2 diabetes.FEBS letters · 2025Review
- Diabetes mellitus polygenic risk scores: heterogeneity and clinical translation.Nature reviews. Endocrinology · 2025Review
- Heterogeneous endocrine cell composition defines human islet functional phenotypes.bioRxiv : the preprint server for biology · 2025Article
- Young-onset type 2 diabetes-Epidemiology, pathophysiology, and management.Journal of diabetes investigation · 2025Review
- Clinical use of polygenic scores in type 2 diabetes: challenges and possibilities.Diabetologia · 2025Review
- Exploring the shared genetic landscape of diabetes and cardiovascular disease: findings and future implications.Diabetologia · 2025Review
- Mapping disease loci to biological processes via joint pleiotropic and epigenomic partitioning.medRxiv : the preprint server for health sciences · 2025Article
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Authors and funding
53 authors at 19 institutions in 5 countries.
Daniel DiCorpoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA.
Jessica LeClairDepartment of Biostatistics, Boston University School of Public Health, Boston, MA.
Joanne B ColePrograms in Metabolism and Medical & Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.
Chloé SarnowskiDepartment of Biostatistics, Boston University School of Public Health, Boston, MA.
Fariba AhmadizarDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.ORCID 0000-0002-6261-9445
Lawrence F BielakDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI.
Anneke BlokstraNational Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
Erwin P BottingerHasso Plattner Institute Digital Health, Potsdam, Germany.
Layal ChakerDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Yii-Der I ChenThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
Ye ChenClinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA.
Paul S de VriesHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX.
Tariq FaquihDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
Mohsen GhanbariDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Valborg GudmundsdottirIcelandic Heart Association, Kopavogur, Iceland.
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
Natalie R HasbaniHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX.
Dorina IbiNational Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
M Arfan IkramDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Maryam KavousiDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.ORCID 0000-0001-5976-6519
Hampton L LeonardLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD.
Aaron LeongPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.ORCID 0000-0002-3248-9547
Josep M MercaderPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.ORCID 0000-0001-8494-3660
Alanna C MorrisonClinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA.
Girish N NadkarniThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.ORCID 0000-0001-6319-4314
Mike A NallsLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD.
Raymond NoordamSection of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.ORCID 0000-0001-7801-809X
Michael PreussThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI.
Stella TrompetSection of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Petra VissinkNational Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
Jie YaoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
Wei ZhaoDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI.
Eric BoerwinkleHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX.
Mark O GoodarziDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.ORCID 0000-0001-6364-5103
Vilmundur GudnasonIcelandic Heart Association, Kopavogur, Iceland.ORCID 0000-0001-5696-0084
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI.
Ruth J F LoosDepartment of Medicine, Harvard Medical School, Boston, MA.
Ching-Ti LiuDepartment of Biostatistics, Boston University School of Public Health, Boston, MA.ORCID 0000-0002-0703-0742
Alisa K ManningClinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA.
Dennis Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
James S PankowDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN.
H Susan J PicavetNational Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
Naveed SattarBritish Heart Foundation Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, U.K.ORCID 0000-0002-1604-2593
Eleanor M SimonsickTranslational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD.
W M Monique VerschurenNational Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
Ko Willems van DijkDepartment of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Jose C FlorezDepartment of Medicine, Harvard Medical School, Boston, MA.ORCID 0000-0002-1730-9325
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
James B MeigsPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.ORCID 0000-0002-2439-2657
Josée DupuisDepartment of Biostatistics, Boston University School of Public Health, Boston, MA.
Miriam S UdlerPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.ORCID 0000-0003-3824-9162
Leiden University Medical Center · NLBoston University · USBroad Institute · USUCLA Medical Center · USErasmus MC · NLUniversity of Michigan · USHarvard University · USNational Institute for Public Health and the Environment · NLNational Institutes of Health · USIcahn School of Medicine at Mount Sinai · USMassachusetts General Hospital · USThe University of Texas Health Science Center at Houston · USUniversity of Iceland · ISBaylor College of Medicine · USBritish Heart Foundation · GBCedars-Sinai Medical Center · USMount Sinai Health System · USUniversity of Minnesota · USUtrecht University · NL
Funding
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MInstitute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4MWake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MGenome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2MTHE PURPOSE OF MODIFICATION TO(1)INCREASE EFFORT OF OPTION 2 AND OPTION 3 FOR ICN01AG12100 · NIA · ICELANDIC HEART ASSOCIATION · PI GUDNASON, VILMUNDUR · 2007 to 2012
$18.4MTask Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2MEpidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8MThe Family Blood Pressure Program (GENOA Network)U01HL054481 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A · 2000 to 2007
$6.7MHispanic Latino Lipid ConsortiumR01HL142302 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jennifer Below, JOSEPH MCCORMICK · 2018 to 2026
$5.8MMedical Research Council MC_PC_17228Medical Research Council MC_QA137853NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NCRR NIH HHS UL1 RR025005NHGRI NIH HHS R56 HG010297NHGRI NIH HHS U01 HG004402NHGRI NIH HHS U01 HG007417NHGRI NIH HHS U01 HG011723NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS HHSN268201700001CNHLBI NIH HHS HHSN268201700001INHLBI NIH HHS HHSN268201700002CNHLBI NIH HHS HHSN268201700002INHLBI NIH HHS HHSN268201700003CNHLBI NIH HHS HHSN268201700003INHLBI NIH HHS HHSN268201700004CNHLBI NIH HHS HHSN268201700004INHLBI NIH HHS HHSN268201700005CNHLBI NIH HHS HHSN268201700005INHLBI NIH HHS K24 HL157960NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N02 HL064278NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01 HL087660NHLBI NIH HHS R01 HL119443NHLBI NIH HHS R01 HL142302NHLBI NIH HHS R01 HL151855NHLBI NIH HHS U01 HL054457NHLBI NIH HHS U01 HL054464NHLBI NIH HHS U01 HL054481NHLBI NIH HHS U10 HL054457NHLBI NIH HHS U10 HL054464NHLBI NIH HHS U10 HL054481NIA NIH HHS K99 AG066849NIA NIH HHS N01AG12100NIA NIH HHS R00 AG066849NIA NIH HHS R01 AG028050NIDA NIH HHS HHSN271201200022CNIDDK NIH HHS K23 DK107908NIDDK NIH HHS K23 DK114551NIDDK NIH HHS K99 DK127196NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK078616NIDDK NIH HHS R01 DK107786NIDDK NIH HHS R01 DK110113NIDDK NIH HHS R01 DK127139NIDDK NIH HHS R03 DK118305NIDDK NIH HHS R56 DK126930NIDDK NIH HHS U01 DK078616NIDDK NIH HHS UM1 DK078616NIGMS NIH HHS T32 GM074905NINR NIH HHS R01 NR012459
Abstract
objectiveType 2 diabetes (T2D) has heterogeneous patient clinical characteristics and outcomes. In previous work, we investigated the genetic basis of this heterogeneity by clustering 94 T2D genetic loci using their associations with 47 diabetes-related traits and identified five clusters, termed β-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. The relationship between these clusters and individual-level metabolic disease outcomes has not been assessed. RESEARCH DESIGN AND
methodsHere we constructed individual-level partitioned polygenic scores (pPS) for these five clusters in 12 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (n = 454,193) and tested for cross-sectional association with T2D-related outcomes, including blood pressure, renal function, insulin use, age at T2D diagnosis, and coronary artery disease (CAD).
resultsDespite all clusters containing T2D risk-increasing alleles, they had differential associations with metabolic outcomes. Increased obesity and lipodystrophy cluster pPS, which had opposite directions of association with measures of adiposity, were both significantly associated with increased blood pressure and hypertension. The lipodystrophy and liver/lipid cluster pPS were each associated with CAD, with increasing and decreasing effects, respectively. An increased liver/lipid cluster pPS was also significantly associated with reduced renal function. The liver/lipid cluster includes known loci linked to liver lipid metabolism (e.g., GCKR, PNPLA3, and TM6SF2), and these findings suggest that cardiovascular disease risk and renal function may be impacted by these loci through their shared disease pathway.
conclusionsOur findings support that genetically driven pathways leading to T2D also predispose differentially to clinical outcomes.
Indexed as
Diabetes Mellitus, Type 2Pharmaceutical PreparationsAllelesCross-Sectional StudiesGenetic LociHumansObesityPharmaceutical Preparations
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