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Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells.
Chen, Lu; Ge, Bing; Casale, Francesco Paolo; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yan, Ying; Kundu, Kousik; Ecker, Simone; Datta, Avik; Richardson, David; Burden, Frances; Mead, Daniel; Mann, Alice L; Fernandez, Jose Maria; Rowlston, Sophia; Wilder, Steven P; Farrow, Samantha; Shao, Xiaojian; Lambourne, John J; Redensek, Adriana; Albers, Cornelis A; Amstislavskiy, Vyacheslav; Ashford, Sofie; Berentsen, Kim; Bomba, Lorenzo; Bourque, Guillaume; Bujold, David; Busche, Stephan; Caron, Maxime; Chen, Shu-Huang; Cheung, Warren; Delaneau, Oliver; Dermitzakis, Emmanouil T; Elding, Heather; Colgiu, Irina; Bagger, Frederik O; Flicek, Paul; Habibi, Ehsan; Iotchkova, Valentina; Janssen-Megens, Eva; Kim, Bowon; Lehrach, Hans; Lowy, Ernesto; Mandoli, Amit; Matarese, Filomena; Maurano, Matthew T; Morris, John A; Pancaldi, Vera.
Affiliation
  • Chen L; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
  • Ge B; Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada.
  • Casale FP; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Vasquez L; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.
  • Kwan T; Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada.
  • Garrido-Martín D; Bioinformatics and Genomics, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Carrer del Dr. Aiguader, 88, Barcelona 8003, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Plaça de la Mercè, 10- 12, Barcelona 8002, Spain.
  • Watt S; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.
  • Yan Y; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.
  • Kundu K; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
  • Ecker S; Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro, 3, Madrid 28029, Spain; UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6BT, UK.
  • Datta A; Vertebrate Genomics, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Richardson D; Vertebrate Genomics, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Burden F; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
  • Mead D; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.
  • Mann AL; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.
  • Fernandez JM; Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro, 3, Madrid 28029, Spain.
  • Rowlston S; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
  • Wilder SP; Genome Analysis, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Farrow S; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
  • Shao X; Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada.
  • Lambourne JJ; Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge
  • Redensek A; Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada.
  • Albers CA; Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, P.O. Box 9101, Nijmegen 6500 HB, the Netherlands; Molecular Developmental Biology, Radboud Institute for Life Sciences, Radboud University, P.O. Box 9101, Nijmegen 6500 HB, the Netherlands.
  • Amstislavskiy V; Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestr. 63/73, Berlin 14195, Germany.
  • Ashford S; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
  • Berentsen K; Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen 6525GA, the Netherlands.
  • Bomba L; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.
  • Bourque G; Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada.
  • Bujold D; Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada.
  • Busche S; Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada.
  • Caron M; Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada.
  • Chen SH; Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada.
  • Cheung W; Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada.
  • Delaneau O; Genetic Medicine and Development, University of Geneva Medical School-CMU, 1 Rue Michel-Servet, Geneva 1211, Switzerland.
  • Dermitzakis ET; Genetic Medicine and Development, University of Geneva Medical School-CMU, 1 Rue Michel-Servet, Geneva 1211, Switzerland.
  • Elding H; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.
  • Colgiu I; Human Genetics Informatics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.
  • Bagger FO; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK; National Health Service (NHS) Blood and Transplant, Ca
  • Flicek P; Vertebrate Genomics, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Habibi E; Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen 6525GA, the Netherlands.
  • Iotchkova V; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Janssen-Megens E; Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen 6525GA, the Netherlands.
  • Kim B; Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen 6525GA, the Netherlands.
  • Lehrach H; Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestr. 63/73, Berlin 14195, Germany.
  • Lowy E; Vertebrate Genomics, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Mandoli A; Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen 6525GA, the Netherlands.
  • Matarese F; Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen 6525GA, the Netherlands.
  • Maurano MT; Institute for Systems Genetics, New York University Langone Medical Center, ACLS West, Room 511, 430 East 29(th) Street, New York, NY 10016, USA.
  • Morris JA; Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada.
  • Pancaldi V; Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro, 3, Madrid 28029, Spain.
Cell ; 167(5): 1398-1414.e24, 2016 11 17.
Article in En | MEDLINE | ID: mdl-27863251
ABSTRACT
Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14+ monocytes, CD16+ neutrophils, and naive CD4+ T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of cis-genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies. Further, we characterize highly coordinated genetic effects on gene expression, methylation, and histone variation through quantitative trait locus (QTL) mapping and allele-specific (AS) analyses. Finally, we demonstrate colocalization of molecular trait QTLs at 345 unique immune disease loci. This expansive, high-resolution atlas of multi-omics changes yields insights into cell-type-specific correlation between diverse genomic inputs, more generalizable correlations between these inputs, and defines molecular events that may underpin complex disease risk.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transcription, Genetic / Monocytes / T-Lymphocytes / Epigenomics / Immune System Diseases / Neutrophils Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: En Journal: Cell Year: 2016 Type: Article Affiliation country: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transcription, Genetic / Monocytes / T-Lymphocytes / Epigenomics / Immune System Diseases / Neutrophils Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: En Journal: Cell Year: 2016 Type: Article Affiliation country: United kingdom