SynthesisNature genetics2020
Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis.
Registry-linked trialOpen access · greenAbstract readMeta-Analysis
In one paragraph
Synthesis in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05166447 (Twenty-year Follow-up of the Inter99 Cohort), which is not on this map. Cited by 506 papers, 10 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
506citing papers in PubMed, 10 pooled it
85.5field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
NCT05166447 enrolling by invitationnot on this mapstarted 2021, after this paper: background citation
Twenty-year Follow-up of the Inter99 Cohort
Who cites it
506 citing papers in PubMed, 10 syntheses or guidelines pooled it, 775 citations in OpenAlex.
- Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.The lancet. Diabetes & endocrinology · 2026Pooled it
- Multi-ancestry, trans-generational GWAS meta-analysis of gestational diabetes and glycaemic traits during pregnancy reveals limited evidence of pregnancy-specific genetic effects.Nature communications · 2026Pooled it
- Association of CDKAL1 rs7754840 with gestational diabetes mellitus: a systematic review and meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Meta-evolutionary exome analysis identifies novel type 2 diabetes mellitus genes in the UK Biobank and all of us.PLoS genetics · 2025Pooled it
- A contextual genomic perspective on physical activity and its relationship to health, well being and illness.Nature genetics · 2025Pooled it
- Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.Nature communications · 2025Pooled it
- Polymorphic variants and risk of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: systematic review and meta-analysis.BMC endocrine disorders · 2025Pooled it
- Associations Between TCF7L2, PPARγ, and KCNJ11 Genotypes and Insulin Response to an Oral Glucose Tolerance Test: A Systematic Review.Molecular nutrition & food research · 2025Pooled it
- Deep learning and genome-wide association meta-analyses of bone marrow adiposity in the UK Biobank.Nature communications · 2025Pooled it
- Identification of susceptibility loci and relevant cell type for IgA nephropathy in Han Chinese by integrative genome-wide analysis.Frontiers of medicine · 2024Pooled it
- Decomposing population differences in type 2 diabetes through a high-resolution GWAS of ~600,000 individuals with East Asian ancestry.Communications biology · 2026Article
- Immunometabolism in Obesity-Associated Type 2 Diabetes: Molecular Mechanisms and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Protein mediators of chronic kidney disease in Type 2 diabetes: A mendelian randomization study.PLoS medicine · 2026Article
- Resistant Hypertension Variants Link to Hyperaldosteronism and Potassium Levels.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Multimodal deep learning enhances genomic risk prediction for cardiometabolic diseases.Briefings in bioinformatics · 2026Article
- New Genetic Associations Between Alzheimer's Disease and Its Key Risk Factors.Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society · 2026Article
- Expanding CIRdb, a comprehensive catalog of whole-exome sequencing data of Canary Islanders.iScience · 2026Article
- Single-nucleus analysis of human white adipose tissue reveals adipocyte subsets with distinct metabolic profiles.Nature communications · 2026Article
- The Potential Physiologic Mechanisms by Which Early-Life Nutrition May Influence Type 2 Diabetes Pathophysiology in Humans.Annual review of nutrition · 2026Review
- Artificial intelligence-enhanced electrocardiography for the prediction of future type 2 diabetes mellitus: a model-development and multicentre validation study.European heart journal. Digital health · 2026Article
446 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
50 authors at 20 institutions in 5 countries.
Marijana Vujkovic *Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4924-5714
Jacob M Keaton *Biomedical Laboratory Research and Development, Tennessee Valley Healthcare System, Nashville, TN, USA.
Julie A LynchVA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0003-0108-2127
Donald R MillerEdith Nourse Rogers Memorial VA Hospital, Bedford, MA, USA.
Jin ZhouPhoenix VA Health Care System, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0001-7983-0274
Catherine TcheandjieuVA Palo Alto Health Care System, Palo Alto, CA, USA.
Jennifer E HuffmanVA Boston Healthcare System, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9672-2491
Themistocles L AssimesVA Palo Alto Health Care System, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-2349-0009
Kimberly LorenzCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8674-2942
Xiang ZhuVA Palo Alto Health Care System, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-1134-6413
Austin T HilliardVA Palo Alto Health Care System, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0002-1289-4377
Renae L JudyCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Jie HuangVA Boston Healthcare System, Boston, MA, USA.
Kyung M LeeVA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0001-8995-0448
Derek KlarinVA Boston Healthcare System, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4636-5780
Saiju PyarajanVA Boston Healthcare System, Boston, MA, USA.
John DaneshDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Olle MelanderDepartment of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Asif RasheedCenter for Non-Communicable Diseases, Karachi, Sindh, Pakistan.
Nadeem H MallickPunjab Institute of Cardiology, Lahore, Punjab, Pakistan.ORCID http://orcid.org/0000-0002-8789-147X
Shahid HameedPunjab Institute of Cardiology, Lahore, Punjab, Pakistan.
Irshad H QureshiDepartment of Medicine, King Edward Medical University, Lahore, Punjab, Pakistan.
Muhammad Naeem AfzalDepartment of Medicine, King Edward Medical University, Lahore, Punjab, Pakistan.
Uzma MalikDepartment of Medicine, King Edward Medical University, Lahore, Punjab, Pakistan.
Anjum JalalDepartment of Cardiology, Faisalabad Institute of Cardiology, Faisalabad, Punjab, Pakistan.
Shahid AbbasDepartment of Cardiology, Faisalabad Institute of Cardiology, Faisalabad, Punjab, Pakistan.
Xin ShengDepartment of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3620-3577
Long GaoDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Klaus H KaestnerDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Katalin SusztakDepartment of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1005-3726
Yan V SunAtlanta VA Medical Center, Decatur, GA, USA.ORCID http://orcid.org/0000-0002-2838-1824
Scott L DuVallVA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0002-4898-3865
Kelly ChoVA Boston Healthcare System, Boston, MA, USA.
Jennifer S LeeVA Palo Alto Health Care System, Palo Alto, CA, USA.
J Michael GazianoVA Boston Healthcare System, Boston, MA, USA.
Lawrence S PhillipsAtlanta VA Medical Center, Decatur, GA, USA.ORCID http://orcid.org/0000-0002-6542-8046
James B MeigsProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Peter D ReavenPhoenix VA Health Care System, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0001-8923-6690
Peter W WilsonAtlanta VA Medical Center, Decatur, GA, USA.
Todd L EdwardsVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-4318-6119
Daniel J RaderDepartment of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9245-9876
Scott M DamrauerCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8009-1632
Christopher J O'DonnellVA Boston Healthcare System, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2667-8624
Philip S TsaoVA Palo Alto Health Care System, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0001-7274-9318
HPAP Consortium
Regeneron Genetics Center
VA Million Veteran Program
Kyong-Mi Chang *Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-6811-9364
Benjamin F Voight *Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA. bvoight@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0002-6205-9994
Danish Saleheen *Center for Non-Communicable Diseases, Karachi, Sindh, Pakistan. ds3792@cumc.columbia.edu.ORCID http://orcid.org/0000-0001-6193-020X
Regeneron (United States) · USVA Boston Healthcare System · USBrigham and Women's Hospital · USUniversity of Pennsylvania · USVA Palo Alto Health Care System · USThe University of Texas Health Science Center at San Antonio · USEmory University · USKing Edward Medical University · PKPhiladelphia VA Medical Center · USVA Connecticut Healthcare System · USVA Salt Lake City Healthcare System · USVA Tennessee Valley Healthcare System · USBay Pines VA Healthcare System · USBirmingham VA Medical Center · USBroad Institute · USColumbia University Irving Medical Center · USEdith Nourse Rogers Memorial Veterans Hospital · USEdward Hines, Jr. VA Hospital · USHarvard University · USHunter Holmes McGuire VA Medical Center · US
Funding
Glycemia Reduction Approaches in Diabetes: A comparative effectiveness studyU01DK098246 · NIDDK · GEORGE WASHINGTON UNIVERSITY · PI KRAUSE-STEINRAUF, HEIDI, LACHIN, JOHN M · 2012 to 2022
$238.9MSOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI DEAN BILLHEIMER · 1994 to 2026
$36.7MPenn integrated Human Pancreas procurement and Analysis ProgramUC4DK112217 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI BETTS, MICHAEL R, FELDMAN, MICHAEL D · 2016 to 2020
$17.8MTranslational Research Core - Engagement and Behavior ChangeP30DK111024 · NIDDK · EMORY UNIVERSITY · PI Mohammed Kumail Ali · 2016 to 2026
$13.4MHARVARD-LONGWOOD RESEARCH TRAINING IN VASCULAR SURGERYT32HL007734 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FERRAN, CHRISTIANE, LOGERFO, FRANK W · 1993 to 2023
$10.5MProteomics CoreP30DK123704 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DON C. ROCKEY · 2020 to 2026
$8.8MEpigenetics of Chronic Kidney DiseaseR01DK087635 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KATALIN SUSZTAK · 2009 to 2026
$7.0MTOPMed Omics of Type 2 Diabetes and Quantitative TraitsUM1DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MANNING, ALISA KNODLE · 2021 to 2025
$3.8MNetwork-based algorithms for target identification and drug repositioning from genetic associationsR01HG010067 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI GREENE, CASEY S · 2018 to 2022
$3.2MAlgorithms to identify non-coding mutational burden and disease-relevant pathwaysR01DK101478 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI VOIGHT, BENJAMIN FRANKLIN · 2014 to 2018
$2.9MVitamin D for Type 2 Diabetes (D2D trial)U34DK091958 · NIDDK · TUFTS MEDICAL CENTER · PI PITTAS, ANASTASSIOS G · 2011 to 2012
$792kReach, Outcomes and System Impacts of the VA's National Weight Loss Program, MOVER21DK099716 · NIDDK · EMORY UNIVERSITY · PI PHILLIPS, LAWRENCE S · 2014 to 2015
$321kBLRD VA I01 BX003362BLRD VA I01 BX004821CSRD VA I01 CX001025CSRD VA I01 CX001737CSRD VA IK2 CX001780NHGRI NIH HHS R01 HG010067NHLBI NIH HHS T32 HL007734NIAID NIH HHS R03 AI133172NIDDK NIH HHS P30 DK111024NIDDK NIH HHS P30 DK123704NIDDK NIH HHS R01 DK087635NIDDK NIH HHS R01 DK101478NIDDK NIH HHS R21 DK099716NIDDK NIH HHS R56 DK101478NIDDK NIH HHS U01 DK098246NIDDK NIH HHS U34 DK091958NIDDK NIH HHS UC4 DK112217NIDDK NIH HHS UM1 DK078616NIEHS NIH HHS P30 ES006694
Abstract
We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ancestry meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP), DIAMANTE, Biobank Japan and other studies. We report 568 associations, including 286 autosomal, 7 X-chromosomal and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis detected 3,568 T2D associations with genetically predicted gene expression in 687 novel genes; of these, 54 are known to interact with FDA-approved drugs. A polygenic risk score (PRS) was strongly associated with increased risk of T2D-related retinopathy and modestly associated with chronic kidney disease (CKD), peripheral artery disease (PAD) and neuropathy. We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including coronary heart disease (CHD), CKD, PAD and neuropathy. These findings may help to identify potential therapeutic targets for T2D and genomic pathways that link T2D to vascular outcomes.
Indexed as
Genetic Predisposition to DiseaseBlack or African AmericanChromosomes, Human, XDiabetes ComplicationsDiabetes Mellitus, Type 2Diabetic AngiopathiesEuropeFemaleGenetic Association StudiesHumansHypoglycemic AgentsMalePolymorphism, Single NucleotideRisk AssessmentHypoglycemic Agents
Identifiers
What OpenQuestion holds
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Registered trials
NCT05166447ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.