دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: TIGER: The gene expression regulatory variation landscape of human pancreatic islets.
المؤلفون: Alonso L; Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain., Piron A; ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels 1070, Belgium; Interuniversity Institute of Bioinformatics in Brussels (IB2), Brussels 1050, Belgium., Morán I; Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain., Guindo-Martínez M; Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain., 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., 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., 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., Royo R; Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain., Puiggròs M; Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain., 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., Suleiman M; Department of Clinical and Experimental Medicine and AOUP Cisanello University Hospital, University of Pisa, Pisa 56126, Italy., Marselli L; Department of Clinical and Experimental Medicine and AOUP Cisanello University Hospital, University of Pisa, Pisa 56126, Italy., Esguerra JLS; Unit of Islet Cell Exocytosis, Lund University Diabetes Centre, Malmö 214 28, Sweden., Turatsinze JV; ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels 1070, Belgium., 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., Nylander V; Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK., Chen J; Exeter Centre of Excellence for Diabetes Research (EXCEED), University of Exeter Medical School, Exeter EX4 4PY, UK., Eliasson L; Unit of Islet Cell Exocytosis, Lund University Diabetes Centre, Malmö 214 28, Sweden., Defrance M; ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels 1070, Belgium., Amela R; Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain., Mulder H; Unit of Molecular Metabolism, Lund University Diabetes Centre, Malmö 214 28, Sweden., 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., 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., Marchetti P; Department of Clinical and Experimental Medicine and AOUP Cisanello University Hospital, University of Pisa, Pisa 56126, Italy., Eizirik DL; ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels 1070, Belgium; WELBIO, Université Libre de Bruxelles, Brussels 1050, Belgium., 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., 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., 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., 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.
مؤلفون مشاركون: MAGIC
المصدر: Cell reports [Cell Rep] 2021 Oct 12; Vol. 37 (2), pp. 109807.
نوع المنشور: Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, c 2012-
مواضيع طبية MeSH: Diabetes Mellitus, Type 2*/genetics , Diabetes Mellitus, Type 2*/metabolism , Genetic Variation* , Genomics* , Islets of Langerhans*/metabolism, Humans ; Cyclin D2/genetics ; Cyclin D2/metabolism ; Databases, Genetic ; Epigenome ; Europe ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Phenotype ; Quantitative Trait Loci ; Transcriptome ; Zinc Transporter 8/genetics ; Zinc Transporter 8/metabolism
مستخلص: 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.
Competing Interests: Declaration of interests A.L.G.’s spouse is an employee of Genentech and holds stock options in Roche.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: U01 DK085545 United States DK NIDDK NIH HHS; U01 DK105535 United States DK NIDDK NIH HHS; 095101 United Kingdom WT_ Wellcome Trust; 203141 United Kingdom WT_ Wellcome Trust; 200837/Z/16/Z United Kingdom WT_ Wellcome Trust; MR/L02036X/1 United Kingdom MRC_ Medical Research Council; 106130 United Kingdom WT_ Wellcome Trust; U01 DK127786 United States DK NIDDK NIH HHS; 200837 United Kingdom WT_ Wellcome Trust; WT101033 United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust
فهرسة مساهمة: Keywords: 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
المشرفين على المادة: 0 (CCND2 protein, human)
0 (Cyclin D2)
0 (SLC30A8 protein, human)
0 (Zinc Transporter 8)
تواريخ الأحداث: Date Created: 20211013 Date Completed: 20220217 Latest Revision: 20240824
رمز التحديث: 20240826
مُعرف محوري في PubMed: PMC8864863
DOI: 10.1016/j.celrep.2021.109807
PMID: 34644572
قاعدة البيانات: MEDLINE
الوصف
تدمد:2211-1247
DOI:10.1016/j.celrep.2021.109807