ArticleNature communications2020
Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D.
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In one paragraph
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 8 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 8 pooled it
22.5field-weighted citation impact, top 1% of its field
What it found
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Who cites it
103 citing papers in PubMed, 8 syntheses or guidelines pooled it, 157 citations in OpenAlex.
- Skeletal muscle eQTL meta-analysis implicates genes in the genetic architecture of muscular and cardiometabolic traits.American journal of human genetics · 2025Pooled it
- Sex-stratified genome-wide association meta-analysis of major depressive disorder.Nature communications · 2025Pooled it
- Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.Nature communications · 2025Pooled it
- Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.Nature genetics · 2022Pooled it
- Identification of genetic effects underlying type 2 diabetes in South Asian and European populations.Communications biology · 2022Pooled it
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- TIGER: The gene expression regulatory variation landscape of human pancreatic islets.Cell reports · 2021Pooled it
- Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity.The Journal of clinical endocrinology and metabolism · 2021Pooled it
- Converging TCF7L2 and CDKAL1 pathways in the pathogenesis of type 2 diabetes mellitus.Acta diabetologica · 2026Review
- Utilizing single-cell data for per-cell type eQTL mapping in the human pancreas.bioRxiv : the preprint server for biology · 2026Article
- Article
- Multi-tissue analyses of allele-specific chromatin accessibility nominate likely functional variants for type 2 diabetes.medRxiv : the preprint server for health sciences · 2026Article
- From pancreas and islet resources to diabetes insights.Diabetologia · 2026Review
- Multi-tissue multi-omics integration reveals tissue-specific pathways, gene networks and drug candidates for type 1 diabetes.Diabetologia · 2026Article
- Disentangling adiposity-related and non-adiposity-related genetic pathways for type 2 diabetes.medRxiv : the preprint server for health sciences · 2026Article
- Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects.The EMBO journal · 2026Article
- Heterogeneous endocrine cell composition defines human islet functional phenotypes.Nature communications · 2026Article
- eQTL analysis: A bridge from genome to mechanism.Genes & diseases · 2026Review
- The Genetic Landscape of Diabetes Mellitus: Lessons from Monogenic and Polygenic Forms.Life (Basel, Switzerland) · 2026Review
- Bridging the variant-to-function gap in type 2 diabetes: advances and challenges.Diabetologia · 2026Review
43 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
36 authors at 11 institutions in 9 countries.
Ana Viñuela *Department of Genetic Medicine and Development, University of Geneva Medical School, 1211, Geneva, Switzerland. ana.vinuela@newcastle.ac.uk.ORCID http://orcid.org/0000-0003-3771-8537
Arushi Varshney *Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.ORCID http://orcid.org/0000-0001-9177-9707
Martijn van de Bunt *Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.
Rashmi B Prasad *Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.ORCID http://orcid.org/0000-0002-4400-6741
Olof AsplundLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
Amanda BennettWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.ORCID http://orcid.org/0000-0003-2140-8710
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.ORCID http://orcid.org/0000-0002-6442-7754
Andrew A BrownDepartment of Genetic Medicine and Development, University of Geneva Medical School, 1211, Geneva, Switzerland.
Michael R ErdosMedical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-6603-1833
João FadistaLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
Ola HanssonLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.ORCID http://orcid.org/0000-0002-7394-7639
Gad HatemLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
Cédric HowaldDepartment of Genetic Medicine and Development, University of Geneva Medical School, 1211, Geneva, Switzerland.
Apoorva K IyengarDepartment of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
Paul JohnsonWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.
Ulrika KrusLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
Patrick E MacDonaldDepartment of Pharmacology and Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
Anubha MahajanWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.ORCID http://orcid.org/0000-0001-5585-3420
Jocelyn E Manning FoxDepartment of Pharmacology and Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
Narisu NarisuMedical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-8483-1156
Vibe NylanderOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 7LE, UK.
Peter OrchardDepartment of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
Nikolay OskolkovLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.ORCID http://orcid.org/0000-0001-5326-8893
Nikolaos I PanousisDepartment of Genetic Medicine and Development, University of Geneva Medical School, 1211, Geneva, Switzerland.
Anthony PayneWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.
Michael L StitzelThe Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA.ORCID http://orcid.org/0000-0001-5630-559X
Swarooparani VadlamudiDepartment of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
Ryan WelchDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.ORCID http://orcid.org/0000-0001-6378-1295
Francis S CollinsMedical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-1023-7410
Karen L MohlkeDepartment of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID http://orcid.org/0000-0001-6721-153X
Anna L GloynWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.ORCID http://orcid.org/0000-0003-1205-1844
Laura J ScottDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.ORCID http://orcid.org/0000-0002-4886-5084
Emmanouil T DermitzakisDepartment of Genetic Medicine and Development, University of Geneva Medical School, 1211, Geneva, Switzerland.ORCID http://orcid.org/0000-0002-9302-6490
Leif GroopLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.ORCID http://orcid.org/0000-0002-0187-3263
Stephen C J ParkerDepartment of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
Mark I McCarthyWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK. mccarthy.mark@gene.com.ORCID http://orcid.org/0000-0002-4393-0510
Centre for Human Genetics · GBUniversity of Michigan · USLund University · SEUniversity of Geneva · CHNational Institutes of Health · USUniversity of North Carolina at Chapel Hill · USUniversity of Alberta · CAUniversity of Helsinki · FIJackson Laboratory · USStatens Serum Institut · DKUniversity of Oxford · GB
Funding
Genetic analysis of type II diabetes in Finnish populationZIAHG000024 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI ERDOS, MICHAEL · 2009 to 2025
$38.2MRegional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3MUniversity of Michigan Training Program in Genomic ScienceT32HG000040 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sebastian Zoellner · 1995 to 2026
$16.4MIdentifying 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
$11.3MIdentifying 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
$6.2MContext-specific and combinatorial genetic regulatory grammars in diabetesR01DK117960 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Stephen CJ Parker · 2018 to 2026
$2.8MIdentifying variants causal for Type 2 Diabetes in Major human populationsU01DK085545 · NIDDK · UNIVERSITY OF OXFORD · PI CHAN, JULIANA CN, EBRAHIM, SHAH BRIAN · 2009 to 2013
$2.8MMethods for high-resolution analysis of genetic effects on gene expressionR01MH101814 · NIMH · UNIVERSITY OF GENEVA · PI BUSTAMANTE, CARLOS DANIEL, DERMITZAKIS, EMMANOUIL · 2013 to 2016
$2.3MFunctional genetic variants for type 2 diabetesU01DK105561 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MOHLKE, KAREN L. · 2015 to 2019
$2.3MIntegrating genome-scale data to reveal causal mechanisms in type 2 diabetesU01DK105535 · NIDDK · UNIVERSITY OF OXFORD · PI GLOYN, ANNA LOUISE · 2015 to 2019
$1.7MDepartment of Health NF-SI-0617-10090Intramural NIH HHS Z01 HG000024Intramural NIH HHS ZIA HG000024Medical Research Council MR/L020149/1NHGRI NIH HHS T32 HG000040NIDDK NIH HHS K99 DK092251NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R00 DK092251NIDDK NIH HHS R00 DK099240NIDDK NIH HHS R01 DK062370NIDDK NIH HHS R01 DK072193NIDDK NIH HHS R01 DK117960NIDDK NIH HHS U01 DK062370NIDDK NIH HHS U01 DK085545NIDDK NIH HHS U01 DK105535NIDDK NIH HHS U01 DK105561NIMH NIH HHS R01 MH090941NIMH NIH HHS R01 MH101814Wellcome Trust 090532Wellcome Trust 095101Wellcome Trust 098381Wellcome Trust 106130Wellcome Trust 200837Wellcome Trust 200837/Z/16/ZWellcome Trust 203141Wellcome Trust 212259
Abstract
Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in the stretch enhancers most strongly implicated in GWAS signal location; (c) enrichment of islet cis-eQTL signals with T2D risk variants identified in genome-wide association studies; and (d) colocalization between 47 islet cis-eQTLs and variants influencing T2D or glycemic traits, including DGKB and TCF7L2. Our findings illustrate the advantages of performing functional and regulatory studies in disease relevant tissues.
Indexed as
Genetic Predisposition to DiseaseQuantitative Trait LociAdolescentAdultAgedAged, 80 and overAnimalsBlood GlucoseCell Line, TumorCohort StudiesDiabetes Mellitus, Type 2Diacylglycerol KinaseEnhancer Elements, GeneticFemaleGene Expression RegulationGenome-Wide Association StudyBlood GlucoseDGKD protein, humanDiacylglycerol KinaseTCF7L2 protein, humanTranscription Factor 7-Like 2 Protein
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