Your browser doesn't support javascript.
loading
Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D.
Viñuela, Ana; Varshney, Arushi; van de Bunt, Martijn; Prasad, Rashmi B; Asplund, Olof; Bennett, Amanda; Boehnke, Michael; Brown, Andrew A; Erdos, Michael R; Fadista, João; Hansson, Ola; Hatem, Gad; Howald, Cédric; Iyengar, Apoorva K; Johnson, Paul; Krus, Ulrika; MacDonald, Patrick E; Mahajan, Anubha; Manning Fox, Jocelyn E; Narisu, Narisu; Nylander, Vibe; Orchard, Peter; Oskolkov, Nikolay; Panousis, Nikolaos I; Payne, Anthony; Stitzel, Michael L; Vadlamudi, Swarooparani; Welch, Ryan; Collins, Francis S; Mohlke, Karen L; Gloyn, Anna L; Scott, Laura J; Dermitzakis, Emmanouil T; Groop, Leif; Parker, Stephen C J; McCarthy, Mark I.
Afiliación
  • Viñuela A; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211, Geneva, Switzerland. ana.vinuela@newcastle.ac.uk.
  • Varshney A; Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, 1211, Geneva, Switzerland. ana.vinuela@newcastle.ac.uk.
  • van de Bunt M; Swiss Institute of Bioinformatics, 1211, Geneva, Switzerland. ana.vinuela@newcastle.ac.uk.
  • Prasad RB; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, NE1 4EP, Newcastle, UK. ana.vinuela@newcastle.ac.uk.
  • Asplund O; Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Bennett A; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.
  • Boehnke M; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 7LE, UK.
  • Brown AA; Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, OX3 7LE, UK.
  • Erdos MR; Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
  • Fadista J; Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
  • Hansson O; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.
  • Hatem G; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Howald C; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211, Geneva, Switzerland.
  • Iyengar AK; Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, 1211, Geneva, Switzerland.
  • Johnson P; Swiss Institute of Bioinformatics, 1211, Geneva, Switzerland.
  • Krus U; Population Health and Genomics, University of Dundee, Dundee, Scotland, DD1 9SY, UK.
  • MacDonald PE; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Mahajan A; Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
  • Manning Fox JE; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, DK, 2300, Denmark.
  • Narisu N; Finnish Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.
  • Nylander V; Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
  • Orchard P; Finnish Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.
  • Oskolkov N; Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
  • Panousis NI; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211, Geneva, Switzerland.
  • Payne A; Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, 1211, Geneva, Switzerland.
  • Stitzel ML; Swiss Institute of Bioinformatics, 1211, Geneva, Switzerland.
  • Vadlamudi S; Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
  • Welch R; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.
  • Collins FS; Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
  • Mohlke KL; Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
  • Gloyn AL; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.
  • Scott LJ; Human Genetics, Genentech, 1 DNA Way, South San Francisco, CA, 94080, USA.
  • Dermitzakis ET; Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
  • Groop L; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Parker SCJ; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 7LE, UK.
  • McCarthy MI; Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
Nat Commun ; 11(1): 4912, 2020 09 30.
Article en En | MEDLINE | ID: mdl-32999275
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.
Asunto(s)
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Glucemia / Islotes Pancreáticos / Predisposición Genética a la Enfermedad / Sitios de Carácter Cuantitativo / Diabetes Mellitus Tipo 2 Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Aged80 / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article País de afiliación: Suiza
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Glucemia / Islotes Pancreáticos / Predisposición Genética a la Enfermedad / Sitios de Carácter Cuantitativo / Diabetes Mellitus Tipo 2 Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Aged80 / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article País de afiliación: Suiza