TIGER: The gene expression regulatory variation landscape of human pancreatic islets.

Cyclin D2 / genetics Databases, Genetic Diabetes Mellitus, Type 2 / genetics Epigenome Europe Gene Frequency Genetic Predisposition to Disease Genetic Variation Genome-Wide Association Study Genomics Humans Islets of Langerhans / metabolism Phenotype Quantitative Trait Loci Transcriptome Zinc Transporter 8 / genetics
RNA-seq allele-specific expression beta cell epigenomics expression quantitative trait locus (eQTL) genome-wide association study (GWAS) pancreatic islets regulatory variation transcriptome type 2 diabetes

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
12 10 2021
Historique:
received: 28 05 2021
revised: 23 07 2021
accepted: 16 09 2021
entrez: 13 10 2021
pubmed: 14 10 2021
medline: 19 2 2022
Statut: ppublish

Résumé

Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D.

Identifiants

DOI: 10.1016/j.celrep.2021.109807 PMID: 34644572 PMC: PMC8864863
pubmed: 34644572
pii: S2211-1247(21)01267-5
doi: 10.1016/j.celrep.2021.109807
pmc: PMC8864863
mid: NIHMS1747907
pii:
doi:

Substances chimiques

CCND2 protein, human 0
Cyclin D2 0
SLC30A8 protein, human 0
Zinc Transporter 8 0

Types de publication

Journal Article Meta-Analysis Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

109807

Subventions

Organisme : NIDDK NIH HHS
ID : U01 DK085545
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK105535
Pays : United States
Organisme : Wellcome Trust
ID : 095101
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203141
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 200837/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L02036X/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106130
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : U01 DK127786
Pays : United States
Organisme : Wellcome Trust
ID : 200837
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT101033
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests A.L.G.’s spouse is an employee of Genentech and holds stock options in Roche.

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Auteurs

Lorena Alonso (L)

Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain.

Anthony Piron (A)

ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels 1070, Belgium; Interuniversity Institute of Bioinformatics in Brussels (IB2), Brussels 1050, Belgium.

Ignasi Morán (I)

Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain.

Marta Guindo-Martínez (M)

Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain.

Sílvia Bonàs-Guarch (S)

Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona 08003, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) Barcelona 08013, Spain.

Goutham Atla (G)

Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona 08003, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) Barcelona 08013, Spain.

Irene Miguel-Escalada (I)

Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona 08003, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) Barcelona 08013, Spain.

Romina Royo (R)

Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain.

Montserrat Puiggròs (M)

Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain.

Xavier Garcia-Hurtado (X)

Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona 08003, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) Barcelona 08013, Spain.

Mara Suleiman (M)

Department of Clinical and Experimental Medicine and AOUP Cisanello University Hospital, University of Pisa, Pisa 56126, Italy.

Lorella Marselli (L)

Department of Clinical and Experimental Medicine and AOUP Cisanello University Hospital, University of Pisa, Pisa 56126, Italy.

Jonathan L S Esguerra (JLS)

Unit of Islet Cell Exocytosis, Lund University Diabetes Centre, Malmö 214 28, Sweden.

Jean-Valéry Turatsinze (JV)

ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels 1070, Belgium.

Jason M Torres (JM)

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK.

Vibe Nylander (V)

Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK.

Ji Chen (J)

Exeter Centre of Excellence for Diabetes Research (EXCEED), University of Exeter Medical School, Exeter EX4 4PY, UK.

Lena Eliasson (L)

Unit of Islet Cell Exocytosis, Lund University Diabetes Centre, Malmö 214 28, Sweden.

Matthieu Defrance (M)

ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels 1070, Belgium.

Ramon Amela (R)

Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain.

Hindrik Mulder (H)

Unit of Molecular Metabolism, Lund University Diabetes Centre, Malmö 214 28, Sweden.

Anna L Gloyn (AL)

Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK; Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK; Division of Endocrinology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94304, USA; NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford OX3 7DQ, UK; Stanford Diabetes Research Centre, Stanford University, Stanford, CA 94305, USA.

Leif Groop (L)

Unit of Islet Cell Exocytosis, Lund University Diabetes Centre, Malmö 214 28, Sweden; Unit of Molecular Metabolism, Lund University Diabetes Centre, Malmö 214 28, Sweden; Finnish Institute of Molecular Medicine Finland (FIMM), Helsinki University, Helsinki 00014, Finland.

Piero Marchetti (P)

Department of Clinical and Experimental Medicine and AOUP Cisanello University Hospital, University of Pisa, Pisa 56126, Italy.

Decio L Eizirik (DL)

ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels 1070, Belgium; WELBIO, Université Libre de Bruxelles, Brussels 1050, Belgium.

Jorge Ferrer (J)

Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona 08003, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) Barcelona 08013, Spain; Section of Epigenomics and Disease, Department of Medicine, Imperial College London, London SW7 2AZ, UK.

Josep M Mercader (JM)

Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain; Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. Electronic address: mercader@broadinstitute.org.

Miriam Cnop (M)

ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels 1070, Belgium; Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels 1070, Belgium. Electronic address: mcnop@ulb.ac.be.

David Torrents (D)

Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain. Electronic address: david.torrents@bsc.es.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Cyclines › Cycline D › Cycline D2 › TIGER: The gene expression regulatory...
questionsmedicales.fr › Sciences de l'information › Mémorisation et recherche des informations › Bases de données comme sujet › Bases de données factuelles › Bases de données génétiques › TIGER: The gene expression regulatory...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Diabète de type 2 › TIGER: The gene expression regulatory...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Épigénome › TIGER: The gene expression regulatory...
questionsmedicales.fr › Régions géographiques › Europe › TIGER: The gene expression regulatory...
questionsmedicales.fr › Phénomènes génétiques › Fréquence d'allèle › TIGER: The gene expression regulatory...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › TIGER: The gene expression regulatory...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › TIGER: The gene expression regulatory...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › TIGER: The gene expression regulatory...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › TIGER: The gene expression regulatory...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › TIGER: The gene expression regulatory...
questionsmedicales.fr › Système endocrine › Glandes endocrines › Ilots pancréatiques › TIGER: The gene expression regulatory...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › TIGER: The gene expression regulatory...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Locus génétiques › Locus de caractère quantitatif › TIGER: The gene expression regulatory...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › TIGER: The gene expression regulatory...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Protéines transporteurs de solutés › Transporteur de zinc ZnT-8 › TIGER: The gene expression regulatory...