SynthesisDiabetes2014
Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.
Abstract readMeta-AnalysisReview
In one paragraph
Synthesis in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers, 8 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
199citing papers in PubMed, 8 pooled it
–field-weighted citation impact
What it found
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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.
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Who cites it
199 citing papers in PubMed, 8 syntheses or guidelines pooled it.
- From Molecules to Biomarkers: Nogo Proteins and Receptors in the Early Detection of Type 2 Diabetes Complications: A Systematic Review.International journal of molecular sciences · 2026Pooled 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
- GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.Nature genetics · 2023Pooled it
- Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.Nature genetics · 2018Pooled it
- Genome-wide association study identifies 112 new loci for body mass index in the Japanese population.Nature genetics · 2017Pooled it
- Pooled it
- Pooled it
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- MTNR1B genotype and effects of carbohydrate quantity and dietary glycaemic index on glycaemic response to an oral glucose load: the OmniCarb trial.Diabetologia · 2024Trial
- Trial
- Trial
- Workload-induced changes to cell state contribute to β-cell failure in diabetes.bioRxiv : the preprint server for biology · 2026Article
- Heterogeneous endocrine cell composition defines human islet functional phenotypes.Nature communications · 2026Article
- STARD10 regulates human pancreatic β cell differentiation and triglyceride metabolism.Stem cell reports · 2026Article
- Family history of type 2 diabetes delays development of type 1 diabetes in TEDDY children with islet autoimmunity.Diabetologia · 2026Observational
- Partitioned polygenic scores show mechanistic heterogeneity in type 2 diabetes and hypertension comorbidity.Nature communications · 2026Article
- Opportunistic screening of type 2 diabetes with deep metric learning using electronic health records.Scientific reports · 2025Article
- From Human to Mouse and Back Again: Genetic and Genomic Ta(i)les of Islet Dysfunction in Type 2 Diabetes.Annual review of genetics · 2025Review
- The Pivotal Role of the Western Diet, Hyperinsulinemia, Ectopic Fat, and Diacylglycerol-Mediated Insulin Resistance in Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Diabetes mellitus polygenic risk scores: heterogeneity and clinical translation.Nature reviews. Endocrinology · 2025Review
139 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
65 authors.
Antigone S DimasWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.Alexander Fleming, Biomedical Sciences Research Center, Vari, Athens, Greece.
Vasiliki LagouWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, U.K.
Adam BarkerMedical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K.
Joshua W KnowlesDepartment of Medicine and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA.
Reedik MägiWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, U.K.Estonian Genome Center, University of Tartu, Tartu, Estonia.
Marie-France HivertDepartment of Medicine, Université de Sherbrooke, Sherbrooke, Québec, CanadaGeneral Medicine Division, Massachusetts General Hospital, Boston, MA.
Andrea BenazzoDepartment of Biology and Evolution, University of Ferrara, Ferrara, Italy.
Denis RybinBoston University Data Coordinating Center, Boston, MA.
Anne U JacksonDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI.
Heather M StringhamDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI.
Ci SongDepartment of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, SwedenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Antje Fischer-RosinskyCharité-Universitätsmedizin Berlin, Department of Endocrinology and Metabolism, Berlin, Germany.
Trine Welløv BoesgaardSteno Diabetes Center, Gentofte, Denmark.
Niels GrarupThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Fahim A AbbasiDepartment of Medicine and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA.
Themistocles L AssimesDepartment of Medicine and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA.
Ke HaoDepartment of Genetics and Genomic Sciences, Institute of Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY.
Xia YangDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA.
Cécile LecoeurCNRS UMR8199-Institute of Biology, Pasteur Institute, Lille 2-Droit et Santé University, Lille, France.
Inês BarrosoWellcome Trust Sanger Institute, Hinxton, U.K.University of Cambridge Metabolic Research Laboratories and National Institute for Health Research Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K.
Lori L BonnycastleGenome Technology Branch, National Human Genome Research Institute, Bethesda, MD.
Yvonne BöttcherIFB AdiposityDiseases, Leipzig University Medical Center, Leipzig, Germany.
Suzannah BumpsteadWellcome Trust Sanger Institute, Hinxton, U.K.
Peter S ChinesGenome Technology Branch, National Human Genome Research Institute, Bethesda, MD.
Michael R ErdosGenome Technology Branch, National Human Genome Research Institute, Bethesda, MD.
Jurgen GraesslerDepartment of Medicine III, Division of Prevention and Care of Diabetes, University of Dresden, Dresden, Germany.
Peter KovacsInterdisciplinary Center for Clinical Research Leipzig, Leipzig, Germany.
Mario A MorkenGenome Technology Branch, National Human Genome Research Institute, Bethesda, MD.
Narisu NarisuGenome Technology Branch, National Human Genome Research Institute, Bethesda, MD.
Felicity PayneWellcome Trust Sanger Institute, Hinxton, U.K.
Alena StancakovaDepartment of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Amy J SwiftGenome Technology Branch, National Human Genome Research Institute, Bethesda, MD.
Anke TönjesIFB AdiposityDiseases, Leipzig University Medical Center, Leipzig, GermanyDepartment of Medicine, University of Leipzig, Leipzig, Germany.
Stefan R BornsteinDepartment of Medicine III, Division of Prevention and Care of Diabetes, University of Dresden, Dresden, Germany.
Stéphane CauchiCNRS UMR8199-Institute of Biology, Pasteur Institute, Lille 2-Droit et Santé University, Lille, France.
Philippe FroguelCNRS UMR8199-Institute of Biology, Pasteur Institute, Lille 2-Droit et Santé University, Lille, FranceDepartment of Genomics of Common Disease, Imperial College London, London, U.K.
David MeyreCNRS UMR8199-Institute of Biology, Pasteur Institute, Lille 2-Droit et Santé University, Lille, FranceDepartment of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.
Peter E H SchwarzDepartment of Medicine III, Division of Prevention and Care of Diabetes, University of Dresden, Dresden, Germany.
Hans-Ulrich HäringDepartment of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany.
Ulf SmithLundberg Laboratory for Diabetes Research, Center of Excellence for Metabolic and Cardiovascular Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI.
Richard N BergmanDepartment of Physiology & Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Francis S CollinsGenome Technology Branch, National Human Genome Research Institute, Bethesda, MD.
Karen L MohlkeDepartment of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC.
Jaakko TuomilehtoDiabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, FinlandCentre for Vascular Prevention, Danube University Krems, Krems, AustriaKing Abdulaziz University, Jeddah, Saudi Arabia.
Thomas QuertemousDepartment of Medicine and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA.
Lars LindDepartment of Medical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden.
Torben HansenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkFaculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Oluf PedersenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkHagedorn Research Institute, Copenhagen, DenmarkInstitute of Biomedical Science, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkFaculty of Health Sciences, University of Aarhus, Aarhus, Denmark.
Mark WalkerInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, U.K.
Andreas F H PfeifferCharité-Universitätsmedizin Berlin, Department of Endocrinology and Metabolism, Berlin, GermanyDepartment of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany.
Joachim SprangerCharité-Universitätsmedizin Berlin, Department of Endocrinology and Metabolism, Berlin, Germany.
Michael StumvollIFB AdiposityDiseases, Leipzig University Medical Center, Leipzig, GermanyDepartment of Medicine, University of Leipzig, Leipzig, Germany.
James B MeigsGeneral Medicine Division, Massachusetts General Hospital, Boston, MADepartment of Medicine, Harvard Medical School, Boston, MA.
Nicholas J WarehamMedical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K.
Johanna KuusistoDepartment of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Markku LaaksoDepartment of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Claudia LangenbergMedical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K.
Josée DupuisDepartment of Biostatistics, Boston University School of Public Health, Boston, MAThe National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA.
Richard M WatanabeDepartments of Preventive Medicine and Physiology & Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Jose C FlorezDepartment of Medicine, Harvard Medical School, Boston, MACenter for Human Genetic Research and Diabetes Research Center (Diabetes Unit), Massachusetts General Hospital, Boston, MAProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA.
Erik IngelssonWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Mark I McCarthyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, U.K.Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, U.K.
Inga ProkopenkoWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, U.K.Department of Genomics of Common Disease, Imperial College London, London, U.K.
MAGIC Investigators
Funding
Genetic analysis of type II diabetes in Finnish populationZIAHG000024 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI ERDOS, MICHAEL · 2009 to 2025
$38.2MZD6416 Analgesic--Painful Distal Symmetrical PolyneuropaM01RR001066 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI HALL, JANET E · 1985 to 2008
$37.4MXOLAIR IN SUBJECTS WITH MODERATE TO SEVERE ATOPIC DERMATITIS WITH FOOD ALLERGYM01RR000070 · NCRR · STANFORD UNIVERSITY · PI PARSONNET, JULIE · 1985 to 2008
$32.4MRegional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3MNation Center- Integrative Biomedical Informatics(RMI)U54DA021519 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ATHEY, BRIAN DAVID · 2005 to 2010
$21.3MIdentifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6MTargeted Genetic Analysis of T2D and Quantitative TraitsR01DK072193 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2005 to 2026
$11.3MGenetic epidemiology of rare and regulatory variants for metabolic traitsR01DK093757 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2011 to 2026
$8.2MIdentifying Genes for Type 2 Diabetes:FUSIONR01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2003 to 2025
$6.7MGENETIC ANALYSIS OF TYPE II DIABETES IN FINNISH POPULATIONZ01HG000024 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI COLLINS, FRANCIS S. · 1995 to 2008
$6.2MCommon Genetic Variation and Quantitative Diabetes TraitsR01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2008 to 2014
$5.0MEpidemiology of Precursors to Type 2 DiabetesK24DK080140 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2007 to 2016
$1.9MIntramural NIH HHS Z01 HG000024Medical Research Council G0701863Medical Research Council G1002084Medical Research Council MC_U106179471Medical Research Council MC_UU_12015/1NCRR NIH HHS 2 M01 RR000070NCRR NIH HHS M01 RR000070NCRR NIH HHS M01 RR001066NCRR NIH HHS RR01066NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS N02 HL064278NHLBI NIH HHS N02-HL-6-4278NIDA NIH HHS U54 DA021519NIDDK NIH HHS DK-062370NIDDK NIH HHS DK-069922NIDDK NIH HHS DK-072193NIDDK NIH HHS K24 DK-080140NIDDK NIH HHS K24 DK080140NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R01 DK062370NIDDK NIH HHS R01 DK069922NIDDK NIH HHS R01 DK072193NIDDK NIH HHS R01 DK-078616NIDDK NIH HHS R01 DK078616NIDDK NIH HHS R01 DK093757NIDDK NIH HHS R56 DK062370NIDDK NIH HHS U01 DK062370Wellcome Trust 090532Wellcome Trust 098381
Abstract
Patients with established type 2 diabetes display both β-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.
Indexed as
Genetic Predisposition to DiseaseAllelesCluster AnalysisDiabetes Mellitus, Type 2FemaleGene FrequencyGenetic VariationGenome-Wide Association StudyHumansInsulinInsulin ResistanceInsulin-Secreting CellsInsulin SecretionMalePolymorphism, Single NucleotideQuantitative Trait LociInsulinTranscription Factors
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