2,119 results on '"Broad Institute [Cambridge]"'
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2. A Genome-wide Screen for Genetic Variants Affecting the Expression of Immunologically Relevant Cell Surface Markers
- Author
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De Jager, Philip, Yelensky, Roman, Rossin, Elizabeth, Bonadkar, Sasha, Choy, Edwin, Daly, Mark, Altshuler, David, and Hafler, David
- Published
- 2007
- Full Text
- View/download PDF
3. Wavelet-based techniques for the gamma-ray sky
- Author
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Lee, Samuel [Broad Institute, Cambridge, MA (United States); Princeton Univ., Princeton, NJ (United States)]
- Published
- 2016
- Full Text
- View/download PDF
4. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity
- Author
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Polyak, Kornelia [Dana-Farber Cancer Institute, Boston, MA (United States); Brigham and Women's Hospital, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Harvard Stem Cell Institute, Cambridge, MA (United States); Broad Institute, Cambridge, MA (United States)]
- Published
- 2014
- Full Text
- View/download PDF
5. Evolutionary history of transformation from chronic lymphocytic leukemia to Richter syndrome
- Author
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Erin M. Parry, Ignaty Leshchiner, Romain Guièze, Connor Johnson, Eugen Tausch, Sameer A. Parikh, Camilla Lemvigh, Julien Broséus, Sébastien Hergalant, Conor Messer, Filippo Utro, Chaya Levovitz, Kahn Rhrissorrakrai, Liang Li, Daniel Rosebrock, Shanye Yin, Stephanie Deng, Kara Slowik, Raquel Jacobs, Teddy Huang, Shuqiang Li, Geoff Fell, Robert Redd, Ziao Lin, Binyamin A. Knisbacher, Dimitri Livitz, Christof Schneider, Neil Ruthen, Liudmila Elagina, Amaro Taylor-Weiner, Bria Persaud, Aina Martinez, Stacey M. Fernandes, Noelia Purroy, Annabelle J. Anandappa, Jialin Ma, Julian Hess, Laura Z. Rassenti, Thomas J. Kipps, Nitin Jain, William Wierda, Florence Cymbalista, Pierre Feugier, Neil E. Kay, Kenneth J. Livak, Brian P. Danysh, Chip Stewart, Donna Neuberg, Matthew S. Davids, Jennifer R. Brown, Laxmi Parida, Stephan Stilgenbauer, Gad Getz, Catherine J. Wu, Dana-Farber Cancer Institute [Boston], Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Harvard Medical School [Boston] (HMS), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), CHU Clermont-Ferrand, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Universität Ulm - Ulm University [Ulm, Allemagne], Mayo Clinic [Rochester], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), IBM Thomas J. Watson Research Center, IBM, Moores Cancer Center [La Jolla], School of Medicine [Univ California San Diego] (UC San Diego), University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC), MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Service d'Hématologie [CHRU Nancy], Massachusetts General Hospital [Boston], and Brigham and Women's Hospital [Boston]
- Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,General Medicine ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,General Biochemistry, Genetics and Molecular Biology - Abstract
International audience
- Published
- 2023
- Full Text
- View/download PDF
6. Novel genetic loci underlying human intracranial volume identified through genome-wide association
- Author
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G. Bruce Pike, Marcel P. Zwiers, Andreas Meyer-Lindenberg, Jeroen van der Grond, Randy L. Gollub, Karen A. Mather, Andrew J. Schork, Vidar M. Steen, Marc M. Bohlken, Nhat Trung Doan, Derek W. Morris, John B.J. Kwok, Emma J. Rose, Johanna Hass, Andrew Simmons, Tian Ge, Reinhold Schmidt, Micael Andersson, Ian J. Deary, Christopher Chen, Derrek P. Hibar, Simon E. Fisher, Lucija Abramovic, Marcella Rietschel, Edith Hofer, Simon Lovestone, Clyde Francks, Christopher R.K. Ching, Srdjan Djurovic, Lachlan T. Strike, Lorna M. Lopez, Rene L. Olvera, Owen Carmichael, M. Arfan Ikram, Andre F. Marquand, Christine Macare, W.T. Longstreth, Philippe Amouyel, Aaron L. Goldman, Wolfgang Hoffmann, Philip L. De Jager, David C. Liewald, Harald H H Göring, Aad van der Lugt, David Ames, Neeltje E.M. van Haren, Lars Nyberg, Nina Romanczuk-Seiferth, Lukas Pirpamer, Stefan Ehrlich, Alexa S. Beiser, Lianne Schmaal, Hilkka Soininen, Mark Jenkinson, Kazima B. Bulayeva, Anderson M. Winkler, Mike A. Nalls, Diana Tordesillas-Gutiérrez, Martine Hoogman, Lars T. Westlye, Loes M. Olde Loohuis, Andrew Singleton, Gabriel Cuellar-Partida, Randy L. Buckner, Dorret I. Boomsma, Dena G. Hernandez, Steven G. Potkin, Sudha Seshadri, Bertram Müller-Myhsok, D. Hoehn, Gareth E. Davies, Chantal Depondt, Henrik Walter, Michael E. Weale, Deborah Janowitz, Susanne Erk, Iryna O. Fedko, Daniel R. Weinberger, Nic J A van der Wee, Jean-Luc Martinot, Jessica A. Turner, Marieke Klein, Sandra Barral, Sebastian Mohnke, Albert Hofman, Ingrid Melle, Saud Alhusaini, Vincent Chouraki, Stephen M. Lawrie, Mark E. Bastin, Juan C. Troncoso, Jean Shin, Wiro J. Niessen, Diane M. Becker, Laura Almasy, Anders M. Dale, Benjamin S. Aribisala, Dennis van 't Ent, Marco P. Boks, M. Mallar Chakravarty, Paul M. Thompson, David Reese McKay, Michael Griswold, John Blangero, Narelle K. Hansell, Eco J. C. de Geus, Paul A. Nyquist, Susana Muñoz Maniega, Sampath Arepalli, Tatjana Rundek, Dan L. Longo, Anton J. M. de Craen, Rebekah McWhirter, Nazanin Mirza-Schreiber, Henning Tiemeier, Girma Woldehawariat, Sven Cichon, Irene Pappa, Amelia A. Assareh, Sudheer Giddaluru, Pieter J. Hoekstra, Hieab H.H. Adams, Hilleke E. Hulshoff Pol, Grant W. Montgomery, Roel A. Ophoff, Markus M. Nöthen, Sara Pudas, Sigurdur Sigurdsson, Arthur W. Toga, Tien Yin Wong, Massimo Pandolfo, Corina U. Greven, Esther Walton, Tianye Jia, David J. Stott, Gunter Schumann, Marie-José van Tol, Dalia Kasperaviciute, Thomas Wolfers, Henry Völzke, Ian Ford, Shannon L. Risacher, Jessika E. Sussmann, Nicholas G. Martin, Wei Wen, Daniah Trabzuni, Iwona Kłoszewska, Kwangsik Nho, Gianpiero L. Cavalleri, Adam M. Brickman, Sungeun Kim, Andreas Heinz, Ralph L. Sacco, Neda Jahanshad, Velandai Srikanth, Elena Shumskaya, Susan H. Blanton, Katharina Wittfeld, Badri N. Vardarajan, Joshua C. Bis, Joanne E. Curran, Helena Schmidt, Peter T. Fox, Clifford R. Jack, Jason L. Stein, Laura M. E. Blanken, Thomas Espeseth, Dick J. Veltman, Sebastian Guelfi, Margaret J. Wright, Norman Delanty, Michael Czisch, Martina Papmeyer, Oscar L. Lopez, Marjolein M. J. Van Donkelaar, Bruce M. Psaty, Jan K. Buitelaar, Sven J. van der Lee, David A. Bennett, Beng-Choon Ho, Oliver Martinez, Wiepke Cahn, Li Shen, J. Wouter Jukema, Janita Bralten, Peter Kochunov, Greig I. Zubicaray, Marcel P. van der Brug, Ching-Yu Cheng, Philipp G. Sämann, Stella Trompet, Roberto Roiz-Santiañez, David C. Glahn, Allissa Dillman, Venkata S. Mattay, Dara M. Cannon, Michael W. Weiner, Christopher D. Whelan, Alexander Teumer, Sylvane Desrivières, Ole A. Andreassen, Thomas E. Nichols, Manuel Mattheisen, Matthias Nauck, René S. Kahn, Albert V. Smith, Colin Smith, Vilmundur Gudnason, Denis A. Evans, Anouk den Braber, Katie L. McMahon, Han G. Brunner, Florian Holsboer, Yuri Milaneschi, Andrew J. Saykin, Jiemin Liao, Vince D. Calhoun, Neelum T. Aggarwal, Dennis van der Meer, Hans J. Grabe, Anita L. DeStefano, Claudia L. Satizabal, Alan B. Zonderman, Alex P. Zijdenbos, Tulio Guadalupe, Ingrid Agartz, Jordan W. Smoller, Allison C. Nugent, Alejandro Arias-Vasquez, Masashi Ikeda, Avram J. Holmes, Brenda W.J.H. Penninx, John Hardy, Herve Lemaitre, Charles DeCarli, Patrizia Mecocci, Catharina A. Hartman, Tomas Axelsson, Oliver Grimm, Irina Filippi, Wayne C. Drevets, Hans van Bokhoven, Miguel E. Rentería, Aiden Corvin, Ryota Kanai, Kristel R. van Eijk, Andrew M. McIntosh, Jouke-Jan Hottenga, Roberto Toro, Lavinia Athanasiu, Joanna M. Wardlaw, Thomas H. Mosley, Mina Ryten, Meike W. Vernooij, Michelle Luciano, Joshua L. Roffman, Rebecca F. Gottesman, Dhananjay Vaidya, Ryota Hashimoto, Mar Matarin, Adaikalavan Ramasamy, Jerome I. Rotter, Ryan L. Muetzel, Konstantinos Arfanakis, Theo G.M. van Erp, Ganesh Chauhan, Xinmin Liu, Tomáš Paus, Emma Sprooten, Christiane Wolf, David S. Knopman, Manon Bernard, Zdenka Pausova, Bryan J. Traynor, Maria C. Valdés Hernández, Robert C. Green, Russell Thomson, Ravi Duggirala, Lisa R. Yanek, Luigi Ferrucci, Bing Xu, Thomas D. Dyer, Thomas H. Wassink, Eric Westman, Jennifer S. Richards, Phil H. Lee, Benno Pütz, Mark R. Cookson, Benedicto Crespo-Facorro, Natalie A. Royle, Bernd Kraemer, Katrin Hegenscheid, Francis J. McMahon, Tatiana Foroud, M. Kamran Ikram, Myriam Fornage, Nanda Rommelse, Saima Hilal, Perminder S. Sachdev, Qiang Chen, Najaf Amin, Lenore J. Launer, Norbert Hosten, Guillén Fernández, Simone Reppermund, Ashley Beecham, Dirk J. Heslenfeld, Masaki Fukunaga, Cornelia M. van Duijn, Clinton B. Wright, Erik G. Jönsson, Sanjay M. Sisodiya, Oliver Gruber, Christophe Tzourio, André G. Uitterlinden, Robert Johnson, Jaap Oosterlaan, Bernard Mazoyer, H. Ronald Zielke, Stephanie Le Hellard, Jingyun Yang, Georg Homuth, Stéphanie Debette, Nicola J. Armstrong, Sarah E. Medland, Henry Brodaty, Beverly G Windham, Gary Donohoe, Rachel M. Brouwer, James T. Becker, Kumar B. Rajan, Daan van Rooij, Thomas W. Mühleisen, Kazutaka Ohi, Peter R. Schofield, Tonya White, Barbara Franke, Unn K. Haukvik, Debra A. Fleischman, J. Raphael Gibbs, Colm McDonald, Anbupalam Thalamuthu, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Keck School of Medicine [Los Angeles], University of Southern California (USC), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Johns Hopkins University (JHU), QIMR Berghofer Medical Research Institute, Leiden University Medical Center (LUMC), Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University of Miami Leonard M. Miller School of Medicine (UMMSM), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, Department of Neurology and Neurosurgery [Montreal], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Royal College of Surgeons in Ireland (RCSI), Umeå University, Illinois Institute of Technology (IIT), Rush University Medical Center [Chicago], University of Edinburgh, Lagos State University (LASU), University of New South Wales [Sydney] (UNSW), Murdoch University, University of Oslo (UiO), Uppsala University, Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Toronto, University of Washington [Seattle], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Columbia University Medical Center (CUMC), Columbia University [New York], Pennington Biomedical Research Center, Louisiana State University (LSU), McGill University = Université McGill [Montréal, Canada], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lieber Institute for Brain Development [Baltimore] (LIBD), University of California [Los Angeles] (UCLA), University of California, Vrije Universiteit Amsterdam [Amsterdam] (VU), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Massachusetts General Hospital [Boston], Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Maison de Solenn [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Bergen (UiB), Haukeland University Hospital, Johns Hopkins University School of Medicine [Baltimore], Universität Heidelberg [Heidelberg], University of Mississippi Medical Center (UMMC), International Max Planck Research School for Language Sciences (IMPRS ), Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Language and Genetics Department [Nijmegen], National University of Singapore (NUS), Medical University Graz, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Yale University [New Haven], University College of London [London] (UCL), Imperial College London, Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Medstar Research Institute, Clinical And Experimental Epilepsy, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], Institute of Human Genetics, University of Bonn, Department of Genomics, Life and Brain Center, Groupe d'imagerie neurofonctionnelle (GIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Dpt of Psychiatry [New Haven], Yale University School of Medicine, Department of Psychiatry, VU University Medical Center [Amsterdam], Department of Psychology [Minneapolis], University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Indiana University System, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Statistical Genetics Group, Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), INSERM, Neuroepidemiology U708, Bordeaux, France, Department of Cognitive Sciences [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, Department of Neurosciences [San Diego], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Queensland Institute of Medical Research, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics, King Faisal Specialist Hospital and Research Centre, Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Depts of Radiology, University of Twente [Netherlands], Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Deutsche Bundesbank, National Institutes of Health [Bethesda] (NIH), General Internal Medicine, Johns Hopkins School of Medicine, Biospective [Montréal], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Department of Clinical Genetics, Department of Medical Parasitology and Mycology, School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-Tehran University of Medical Siences, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The University of Texas Health Science Center at Houston (UTHealth), Texas Biomedical Research Institute [San Antonio, TX], 849 Department of Human Genetics, Dementia Collaborative Research Centre, Centre for Healthy Brain Ageing, Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Université de Lausanne (UNIL), Department of Psychiatry [Boston], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Division of Molecular and Cellular Therapeutics, Metacohorts Consortium, Division of Medical Genetics, University of Basel (Unibas), Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Trinity College Dublin-St. James's Hospital, Department of Materials Science & Metallurgy, University of Cambridge [UK] (CAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], VU University Amsterdam, Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), School of Psychology, University of Queensland, Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Molecular and Cellular Therapeutics, Department of Neurology, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratory of Neurogenetics, Department of Genomics, Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Department of Radiology, Mayo Clinic, Department of Medical and Molecular Genetics, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, Department of Physics, Okayama University, Okayama University, National Institute of Aging, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Public Health Genomics Unit, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Department of Mathematics, University of Colorado, University of Colorado [Boulder], Icelandic Heart Association, Kopavogur, Iceland., Faculty of Medicine, University of Iceland [Reykjavik], Department of Molecular Neurosciences, Institute of Neurology, UCL, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University [Osaka], Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Tohoku University [Sendai], Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Centre for Allergy Research, Karolinska Institutet [Stockholm], Interuniversity Cardiology Institute Netherlands, Institute of Cognitive Neuroscience, School of Psychology, University of Sussex, Brighton BN1 9QH, UK, University of Sussex, Medical University of Łódź (MUL), Mayo Clinic [Rochester], University of Maryland School of Medicine, University of Maryland System-University of Maryland System-University of Maryland [Baltimore County] (UMBC), University of Maryland System, Department of Civil and Structural Engineering, The Hong Kong Polytechnic University [Hong Kong] (POLYU)-The Hong Kong Polytechnic University [Hong Kong] (POLYU), Université de Cergy Pontoise (UCP), Université Paris-Seine, Lymphocyte Cell Biology Unit, Laboratory of Genetics, Laboratoire de Statistique Théorique et Appliquée (LSTA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Psychiatry Institute, Department of Health and Human Services, Department of Life Sciences, Mathematical Sciences Institute (MSI), Australian National University (ANU), Centre for Advanced Imaging, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia (UNIPG), Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Medical Faculty [Mannheim], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, Université de Toulon - UFR Lettres et Sciences Humaines (UTLN UFR LSH), Université de Toulon (UTLN), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Institute of Clinical Chemistry and Laboratory Medicine, Warwick Manufacturing Group [Coventry] (WMG), University of Warwick [Coventry], Department of Statistics [Warwick], Delft University of Technology (TU Delft), Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre (MNI), Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, Group Health Research Institute, Group Health Cooperative, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Cedars-Sinai Medical Center, Centre for Healthy Brain Ageing [Sydney], The University of Sydney, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Department of Medical Biochemistry and Microbiology, Department of Clinical and Experimental Epilepsy, Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Monash University [Melbourne], Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia, University of Tasmania [Hobart, Australia] (UTAS), Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Department of Epidemiology, Laboratory of Neuro Imaging [Los Angeles] (LONI), University of York [York, UK], Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Genentech, Inc. [San Francisco], Departments of Radiology and of Epidemiology [Rotterdam], Psychiatry and Leiden Institute for Brain and Cognition, Department of Neurology [Rotterdam], Institute for Community Medicine, Berlin School of Mind and Brain [Berlin], Humboldt-Universität zu Berlin, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Centre for Population Health Sciences, Department of Physics [Hong Kong University of Science and Technology], Hong Kong University of Science and Technology (HKUST), Department of Neurobiology, Care Sciences and Society, Research Laboratory for Archaeology & the History of Art, Singapore Eye Research Institute, Singapore National Eye Centre, School of Life Sciences, Arizona State University [Tempe] (ASU), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), Dpt of Pharmacology and Personalised Medicine [Maastricht], Maastricht University [Maastricht], University of Missouri [Columbia] (Mizzou), University of Missouri System, Göttingen Zentrum Geowissenschaften, Georg-August-University [Göttingen], Human Genetics Center, Psychiatry, EMGO - Mental health, Amsterdam Neuroscience - Complex Trait Genetics, Anatomy and neurosciences, Klinische Genetica, MUMC+: DA Klinische Genetica (5), RS: FHML non-thematic output, RS: GROW - School for Oncology and Reproduction, RS: GROW - R4 - Reproductive and Perinatal Medicine, Genetica & Celbiologie, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Universidad de Cantabria, Universiteit Leiden, Radboud University [Nijmegen], University of California (UC), Universität Heidelberg [Heidelberg] = Heidelberg University, Universität Bonn = University of Bonn, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Yale School of Medicine [New Haven, Connecticut] (YSM), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), University of California (UC)-University of California (UC), Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), King Faisal Specialist Hospital and Research Centre (KFSH & RC), Universiteit Leiden-Universiteit Leiden, University of Twente, University of California [Irvine] (UC Irvine), Radboud University [Nijmegen]-Radboud University [Nijmegen], Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Università degli Studi di Perugia = University of Perugia (UNIPG), University Hospital Mannheim | Universitätsmedizin Mannheim, Universität Leipzig-Universität Leipzig, University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, Harvard University-Massachusetts Institute of Technology (MIT), University of Eastern Finland, Humboldt University Of Berlin, Georg-August-University = Georg-August-Universität Göttingen, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Epidemiology, Child and Adolescent Psychiatry / Psychology, Ophthalmology, Radiology & Nuclear Medicine, Internal Medicine, Neurosciences, Obstetrics & Gynecology, Neurology, EMGO+ - Mental Health, Biological Psychology, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), McGill University-McGill University, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), McGill University, Technische Universität Dresden (TUD), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], University of Bergen (UIB), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Minnesota [Twin Cities], Karakter Child and Adolescent Psychiatry University Center Nijmegen, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Okayama University [Okayama], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], University of Tasmania (UTAS), Humboldt Universität zu Berlin, Department of Physics [Kowloon], University of Missouri [Columbia], Georg-August-Universität Göttingen, and the Alzheimer's Disease Neuroimaging Initiative, EPIGEN, IMAGEN, SYS
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0301 basic medicine ,Netherlands Twin Register (NTR) ,Genome-wide association study ,Disease ,methods [Genome-Wide Association Study] ,Genome-wide association studies ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Cognition ,PARKINSONS-DISEASE ,pathology [Brain] ,genetics [Parkinson Disease] ,610 Medicine & health ,General Neuroscience ,growth & development [Brain] ,physiology [Cognition] ,220 Statistical Imaging Neuroscience ,COMMON VARIANTS ,Brain ,Parkinson Disease ,Phenotype ,17Q21.31 MICRODELETION ,IGF-I ,genetics [Oncogene Protein v-akt] ,Oncogene Protein v-akt ,ALZHEIMERS-DISEASE ,HEAD CIRCUMFERENCE ,Brain size ,genetics [Polymorphism, Single Nucleotide] ,Medical genetics ,GROWTH ,Neuroinformatics ,medicine.medical_specialty ,Neuroscience(all) ,European Continental Ancestry Group ,genetics [Genetic Loci] ,Biology ,Genetic correlation ,Polymorphism, Single Nucleotide ,150 000 MR Techniques in Brain Function ,Article ,White People ,03 medical and health sciences ,Image processing ,SDG 3 - Good Health and Well-being ,ddc:570 ,medicine ,Journal Article ,Humans ,Genetic Predisposition to Disease ,Gene ,METAANALYSIS ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Neurology & Neurosurgery ,Neuroscience (all) ,Height ,[SCCO.NEUR]Cognitive science/Neuroscience ,CONSORTIUM ,Development of the nervous system ,1702 Cognitive Science ,030104 developmental biology ,Genetic Loci ,Human genome ,BRAIN SIZE ,1109 Neurosciences ,genetics [Phosphatidylinositol 3-Kinases] ,Neuroscience ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Contains fulltext : 165723pub.pdf (Publisher’s version ) (Closed access) Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rhogenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
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- 2016
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7. The RBPome of influenza A virus mRNA reveals a role for TDP-43 in viral replication
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Maud Dupont, Tim Krischuns, Quentin Giai-Gianetto, Sylvain Paisant, Stefano Bonazza, Jean-Baptiste Brault, Thibaut Douché, Joel I Perez-Perri, Matthias W Hentze, Stephen Cusack, Mariette Matondo, Catherine Isel, David G Courtney, Nadia Naffakh, Biologie des ARN et virus influenza - RNA Biology of Influenza Virus (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Plateforme de Protéomique / Proteomics platform, Université Paris Cité (UPCité)-Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Wellcome-Wolfson Institute for Experimental Medicine, Queen's University [Belfast] (QUB), European Molecular Biology Laboratory [Heidelberg] (EMBL), European Molecular Biology Laboratory [Grenoble] (EMBL), This work was funded by the Agence Nationale de la Recherche [ANR-18-CE18-0028 to SC and NN, ANR-10-LABX-62IBEID to MM and NN, ANR-21-CE35-0007 to MM], the Marie-Skłodowska Curie Global Fellowship [MSCA-IF-GF:747810 to DGC], and the European Research Council Fellowship [PTFLU 949506 to DGC and SB]. Funding for open access charges [Agence Nationale de la Recherche/ANR-10-LABX-62IBEID], We would like to thank Dr. Feng Zhang (Broad Institute, Cambridge, USA), Dr. Mikhael Matrosovich (Philipps Universität, Marburg, Germany), Dr. Pierre-Olivier Vidalain (CIRI, Lyon), Dr. Daniel Marc (INRAE, Nouzilly, France), Dr. Caroline Demeret, Dr. Sandie Munier and the National Reference Center for Respiratory Viruses (all at Institut Pasteur, Paris, France) and for sharing reagents used in this work. We would like to thank Yves Jacob, Anastasia Komarova and Valérie Najburg (Institut Pasteur, Paris, France) for helpful discussions. Some figures were created with BioRender.com, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-21-CE35-0007,PureMagRupture,Un flux de travail de la gMEP (Genetic magnetic-extraction-proteomics) pour comprendre le lien entre la rupture vacuolaire de Shigella et l'autophagie(2021)
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[SDV]Life Sciences [q-bio] - Abstract
Recent technical advances have significantly improved our understanding of the RNA-binding protein (RBP) repertoire present within eukaryotic cells, with a particular focus on the RBPs that interact with cellular polyadenylated mRNAs. However, recent studies utilising the same technologies have begun to tease apart the RBP interactome of viral mRNAs, notably SARS-CoV-2, revealing both similarities and differences between the RBP profiles of viral and cellular mRNAs. Herein, we comprehensively identified the RBPs that associate with the NP mRNA of an influenza A virus. Moreover, we provide evidence that the viral polymerase is essential for the recruitment of RPBs to viral mRNAs through direct polymerase-RBP interactions during transcription. We show that loss of TDP-43, which associates with the viral mRNAs, results in lower levels of viral mRNAs within infected cells, and a decreased yield of infectious viral particles. Overall, our results uncover an important role for TDP-43 in the influenza A virus replication cycle via a direct interaction with viral mRNAs, and point to a role of the viral polymerase in orchestrating the assembly of viral mRNPs.
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- 2023
8. Multiethnic Genome-Wide Association Study of Cerebral White Matter Hyperintensities on MRI
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Susan H. Blanton, Ashley Beecham, Pamela J. Schreiner, Ralph L. Sacco, Stéphanie Debette, Ben A. Oostra, Marian Beekman, M. Arfan Ikram, Edith Hofer, Anna Maria Töglhofer, Alexander Teumer, Ganesh Chauhan, Clinton B. Wright, Meike W. Vernooij, Wiro J. Niessen, Aad van der Lugt, Cornelia M. van Duijn, Christophe Tzourio, Matthias Nauck, Bernard Mazoyer, Bettina von Sarnowski, Alexa S. Beiser, Susan R. Heckbert, André G. Uitterlinden, Alex P. Zijdenbos, David S. Knopman, Paul Freudenberger, Myriam Fornage, Maaike Schuur, Stephen Turner, Matthew Traylor, Qiong Yang, Fabrice Crivello, P. Eline Slagboom, Ian J. Deary, Sharon L.R. Kardia, Cora E. Lewis, Stella Trompet, Mike A. Nalls, Jennifer A. Smith, Katrin Hegenscheid, Hans J. Grabe, Lenore J. Launer, Reinhold Schmidt, Albert V. Smith, M. Kamran Ikram, Kumar B. Rajan, Mariza de Andrade, Sudha Seshadri, Lorna M. Lopez, Philip L. De Jager, Albert Hofman, Joshua C. Bis, Gerardo Heiss, Neelum T. Aggarwal, Elizabeth J. Atkinson, Carla A. Ibrahim-Verbaas, David C. Liewald, Anton J. M. de Craen, Jing Wang, David J. Stott, Sandra Barral, Adam M. Brickman, Mohamad Habes, Eric Boerwinkle, Katharina Wittfeld, Jerome I. Rotter, Saima Hilal, R. Nick Bryan, Charles C. DeCarli, Mark A. van Buchem, Mitchell S.V. Elkind, Rebecca F. Gottesman, Christiane Wolf, Vincent Chouraki, Jeroen van der Grond, Jiemin Liao, Joris Deelen, Stephen Sidney, Kenneth Rice, Vilmundur Guðnason, Hieab H.H. Adams, Benjamin F.J. Verhaaren, Tien Yin Wong, Oliver Martinez, Denis A. Evans, Helena Schmidt, W. T. Longstreth, J. Wouter Jukema, Richard Mayeux, Joanna M. Wardlaw, Thomas H. Mosley, Michelle Luciano, Sigurdur Sigurdsson, Carole Dufouil, Christopher Chen, Philippe Amouyel, Wei Zhao, John C. van Swieten, Bruce M. Psaty, Hae-Won Uh, B. Gwen Windham, Erasmus University Medical Center [Rotterdam] (Erasmus MC), INSERM U897, University of Bordeaux, France, University of Washington [Seattle], University of Michigan [Ann Arbor], University of Michigan System, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), John P. Hussman Institute for Human Genomics, University of Miami Leonard M. Miller School of Medicine (UMMSM), Rush University Medical Center [Chicago], University of Edinburgh, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands, Depts of Radiology, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Department of Materials Science and Metallurgy [Cambridge University] (DMSM), University of Cambridge [UK] (CAM), JRC Institute for Transuranium Elements [Karlsruhe] (ITU ), European Commission - Joint Research Centre [Karlsruhe] (JRC), Greifswald University Hospital, Division of Biomedical Statistics and Informatics, Mayo Clinic, Division of Biomedical Statistics and Informatics, Mayo Clinic, Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Genetics, The University of Texas Health Science Center at Houston (UTHealth), Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University [New York], Perelman School of Medicine, University of Pennsylvania, INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, Systèmes et Applications des Technologies de l'Information et de l'Energie (SATIE), École normale supérieure - Cachan (ENS Cachan)-Université Paris-Sud - Paris 11 (UP11)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-École normale supérieure - Rennes (ENS Rennes)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE), Department of neurology, Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Dept of Psychology, Molecular Epidemiology, Harvard Medical School [Boston] (HMS), Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Columbia Mailman School of Public Health, Laboratoire pharmaceutique Lilly France [Neuilly-sur-Seine], Institute of Molecular Biology & Biochemistry, Johns Hopkins University School of Medicine [Baltimore], Faculty of Medicine, University of Iceland [Reykjavik], The Icelandic Heart Association, Kopavogur, Iceland, Institutes for Community Medicine, Department of Epidemiology, University of Washington, Group Health Research Institute, Group Health Cooperative, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), National University of Singapore (NUS), Université Grenoble Alpes - UFR Sciences de l'Homme et de la Société (UGA UFR SHS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Grenoble Alpes - UFR Langage, lettres et arts du spectacle, information et communication - Dpt Sciences de l'information et de la communication (UGA UFR LLASIC SIC), Mayo Clinic [Rochester], Academic Unit of Inflammation and Tumour Targeting, Dept. of Oncology, University of Sheffield Medical School, East China University of Science and Technology, Medstar Research Institute, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Bioinformatics, GlaxoSmithKline, National Institutes of Health [Bethesda] (NIH), Institute of Clinical Chemistry and Laboratory Medicine, Universität Greifswald - University of Greifswald, Delft University of Technology (TU Delft), Cardiovascular Health Research Unit, University of Washington, Department of Medicine, University of Washington, Department of Health Services, University of Washington, Department of Biostatistics, University of Washington, Cedars-Sinai Medical Center, Dept of Neurology, Univ Medicine of Greifswald, Germany, Department of Physics [Stockholm], Stockholm University, University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Kaiser Permanente, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Department of Medical Biochemistry and Microbiology, Uppsala University, Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, King‘s College London, Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria, Research Centre for Stroke & Dementia, St George 's Univ of London, Interuniversity Cardiology Institute Netherlands, SAC, Bush Estate, School Medicine, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Singapore Eye Research Institute, Singapore National Eye Centre, University of Oslo (UiO), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ninewells Hospital and Medical School, Biomedical Research Centre, University of Dundee, Dundee Technopole, CXR Biosciences Ltd, Department of Atmospheric, Oceanic, and Space Sciences [Ann Arbor] (AOSS), University of Michigan System-University of Michigan System, University of Miami [Coral Gables], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biospective [Montréal], Dept of Epidemiology & Public Health Sciences, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Mississippi Medical Center (UMMC), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands, Austrian Institute of Technology [Vienna] (AIT), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Human Genetics Center, University of Pennsylvania [Philadelphia], Université Paris-Seine-Université Paris-Seine-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Memory Aging & Cognition Centre, National Univ of Singapore, Singapore, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Dept of Ophthalmology, National Univ of Singapore & National Univ Health System, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), University of California-University of California, Radboud university [Nijmegen], Epidemiology, Radiology & Nuclear Medicine, General Practice, Neurology, Medical Informatics, Clinical Genetics, Internal Medicine, Human genetics, NCA - neurodegeneration, Hal, GIN, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), and HESAM Université (HESAM)-HESAM Université (HESAM)-Centre National de la Recherche Scientifique (CNRS)
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Oncology ,Male ,single nucleotide ,Pathology ,Genome-wide association study ,leukoencephalopathies ,polymorphisms, single nucleotide ,Chromosomes, Human ,Genetics (clinical) ,Aged, 80 and over ,education.field_of_study ,Continental Population Groups ,cerebrovascular disorders ,Middle Aged ,White Matter ,3. Good health ,Stroke ,genetics [Stroke] ,Female ,cerebral small vessel diseases ,Alzheimer's disease ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,hypertension ,Population ,genetics [Chromosomes, Human] ,Article ,Meta-Analysis as Topic ,Internal medicine ,Genetics ,medicine ,Dementia ,Humans ,ddc:610 ,1000 Genomes Project ,education ,Genetic association ,Aged ,Intracerebral hemorrhage ,genome-wide association study ,Models, Genetic ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SCCO.NEUR] Cognitive science/Neuroscience ,Racial Groups ,medicine.disease ,ethnology [Stroke] ,Hyperintensity ,Genetic Loci ,pathology [Stroke] ,business ,polymorphisms ,Genome-Wide Association Study - Abstract
Background— The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. Methods and Results— We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 ( P =2.7×10 −19 ) and identified novel loci on chr10q24 ( P =1.6×10 −9 ) and chr2p21 ( P =4.4×10 −8 ). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 ( P =2.0×10 −8 ) and chr2p16 ( P =1.5×10 −8 ). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). Conclusions— We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.
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- 2015
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9. Gene-lifestyle interactions in the genomics of human complex traits
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Laville, Vincent, Majarian, Timothy, Sung, Yun, Schwander, Karen, Feitosa, Mary, Chasman, Daniel, Bentley, Amy, Rotimi, Charles, Cupples, L., de Vries, Paul, Brown, Michael, Morrison, Alanna, Kraja, Aldi, Province, Mike, Gu, C., Gauderman, W., Working Group, The Charge Gene-Lifestyle Interactions, Rao, D., Manning, Alisa, Aschard, Hugues, Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Washington University in Saint Louis (WUSTL), Washington University School of Medicine in St. Louis, Brigham and Women's Hospital [Boston], National Human Genome Research Institute (NHGRI), Boston University [Boston] (BU), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), The University of Texas Health Science Center at Houston (UTHealth), University of Southern California (USC), The various Gene-Lifestyle Interaction projects, including this summary project, are largely supported by a grant from the U.S. National Heart, Lung, and Blood Institute (NHLBI), the National Institutes of Health, R01HL118305. This work was also supported by the INCEPTION project (PIA/ANR-16-CONV-0005). This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. PSV was supported by American Heart Association grant number 18CDA34110116. YJS was supported by the K25HL121091 award from NHLBI. JG was partly supported by the P01CA196569 grant from the National Institutes of Health., the CHARGE Gene-Lifestyle Interactions Working Group: Vincent Laville, Timothy Majarian, Yun J. Sung, Karen Schwander, Mary F. Feitosa, Daniel I. Chasman, Amy R. Bentley, Charles N. Rotimi, L. Adrienne Cupples, Paul S. de Vries, Michael R. Brown, Alanna C. Morrison, Aldi T. Kraja, Mike Province, C. Charles Gu, W. James Gauderman, D. C. Rao, Alisa K. Manning & Hugues Aschard, and ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016)
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Multifactorial Inheritance ,Phenotype ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Genetics ,Humans ,Epistasis, Genetic ,Gene-Environment Interaction ,Genomics ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,Life Style ,Genetics (clinical) ,Genome-Wide Association Study - Abstract
The role and biological significance of gene-environment interactions in human traits and diseases remain poorly understood. To address these questions, the CHARGE Gene-Lifestyle Interactions Working Group conducted series of genome-wide interaction studies (GWIS) involving up to 610,475 individuals across four ancestries for three lipids and four blood pressure traits, while accounting for interaction effects with drinking and smoking exposures. Here we used GWIS summary statistics from these studies to decipher potential differences in genetic associations and G×E interactions across phenotype-exposure-ancestry combinations, and to derive insights on the potential mechanistic underlying G×E through in-silico functional analyses. Our analyses show first that interaction effects likely contribute to the commonly reported ancestry-specific genetic effect in complex traits, and second, that some phenotype-exposures pairs are more likely to benefit from a greater detection power when accounting for interactions. It also highlighted modest correlation between marginal and interaction effects, providing material for future methodological development and biological discussions. We also estimated contributions to phenotypic variance, including in particular the genetic heritability conditional on the exposure, and heritability partitioned across a range of functional annotations and cell types. In these analyses, we found multiple instances of potential heterogeneity of functional partitions between exposed and unexposed individuals, providing new evidence for likely exposure-specific genetic pathways. Finally, along this work, we identified potential biases in methods used to jointly meta-analyze genetic and interaction effects. We performed simulations to characterize these limitations and to provide the community with guidelines for future G×E studies.
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- 2022
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10. Declines in prevalence alter the optimal level of sexual investment for the malaria parasite Plasmodium falciparum
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Angela M. Early, Flavia Camponovo, Stéphane Pelleau, Gustavo C. Cerqueira, Yassamine Lazrek, Béatrice Volney, Manuela Carrasquilla, Benoît de Thoisy, Caroline O. Buckee, Lauren M. Childs, Lise Musset, Daniel E. Neafsey, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Harvard T.H. Chan School of Public Health, Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Département de Santé Globale - Department Global Health, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Laboratoire de Parasitologie [Cayenne, Guyane française], Laboratoire des Interactions Virus-Hôtes [Cayenne, Guyane Française], Virginia Tech [Blacksburg], This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services, under Grant U19AI110818 to the Broad Institute. This work was supported by an Investissement d’Avenir grant managed by Agence Nationale de la Recherche Centre d’Etude pour la Biodiversité Amazonienne (CEBA[ref. ANR-10-LABX-25-01]), the Santé publique France as National Reference Centre for Malaria, and the French Ministry for Research. F.C. and C.O.B. are supported by a Maximizing Investigators’ Research Award for Early-Stage Investigators (R35 GM-124715). S.P. received funding support from European Commission Grant REGPOT-CT-2011-285837-430 STRonGer. L.M.C. is supported by NSF Standard Grant 1902214., ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), and European Project: 285837,EC:FP7:REGPOT,FP7-REGPOT-2011-1,STRONGER(2011)
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Multidisciplinary ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,genomics ,malaria ,modeling ,sexual commitment ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,adaptation - Abstract
Successful infectious disease interventions can result in large reductions in parasite prevalence. Such demographic change has fitness implications for individual parasites and may shift the parasite’s optimal life history strategy. Here, we explore whether declining infection rates can alter Plasmodium falciparum ’s investment in sexual versus asexual growth. Using a multiscale mathematical model, we demonstrate how the proportion of polyclonal infections, which decreases as parasite prevalence declines, affects the optimal sexual development strategy: Within-host competition in multiclone infections favors a greater investment in asexual growth whereas single-clone infections benefit from higher conversion to sexual forms. At the same time, drug treatment also imposes selection pressure on sexual development by shortening infection length and reducing within-host competition. We assess these models using 148 P. falciparum parasite genomes sampled in French Guiana over an 18-y period of intensive intervention (1998 to 2015). During this time frame, multiple public health measures, including the introduction of new drugs and expanded rapid diagnostic testing, were implemented, reducing P. falciparum malaria cases by an order of magnitude. Consistent with this prevalence decline, we see an increase in the relatedness among parasites, but no single clonal background grew to dominate the population. Analyzing individual allele frequency trajectories, we identify genes that likely experienced selective sweeps. Supporting our model predictions, genes showing the strongest signatures of selection include transcription factors involved in the development of P. falciparum ’s sexual gametocyte form. These results highlight how public health interventions impose wide-ranging selection pressures that affect basic parasite life history traits.
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- 2022
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11. ZNF683 (Hobit) Marks a CD8+ T Cell Population Associated with Anti-Tumor Immunity Following Anti-PD-1 Therapy for Richter Syndrome
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Lemvigh, Camilla, Parry, Erin Michelle, Deng, Stephanie, Dangle, Nathan, Ruthen, Neil, Knisbacher, Binyamin, Broséus, Julien, Hergalant, Sébastien, Guieze, Romain, Li, Shuqiang, Yin, Shanye, Huang, Teddy, Livak, Kenneth, Getz, Gad, Neuberg, Donna, Feugier, Pierre, Kharchenko, Peter, Wierda, William, Olsen, Lars Rønn, Jain, Nitin, Wu, Catherine, Dana-Farber Cancer Institute [Boston], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Harvard Medical School [Boston] (HMS), Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Massachusetts General Hospital [Boston], Service d'Hématologie [CHRU Nancy], MD Anderson Cancer Center [Houston], and The University of Texas Health Science Center at Houston (UTHealth)
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Immunology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Cell Biology ,Hematology ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Biochemistry - Abstract
International audience
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- 2022
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12. Multi-omics insights into the biological mechanisms underlying statistical gene-by-lifestyle interactions with smoking and alcohol consumption
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Timothy D, Majarian, Amy R, Bentley, Vincent, Laville, Michael R, Brown, Daniel I, Chasman, Paul S, de Vries, Mary F, Feitosa, Nora, Franceschini, W James, Gauderman, Casey, Marchek, Daniel, Levy, Alanna C, Morrison, Michael, Province, Dabeeru C, Rao, Karen, Schwander, Yun Ju, Sung, Charles N, Rotimi, Hugues, Aschard, C Charles, Gu, Alisa K, Manning, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), National Institutes of Health [Bethesda] (NIH), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), The University of Texas Health Science Center at Houston (UTHealth), Harvard Medical School [Boston] (HMS), Washington University School of Medicine [Saint Louis, MO], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Southern California (USC), Massachusetts General Hospital [Boston], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], and This work was partly supported by grants R01 HL118305 and R01 HL156991 from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH). This work was also supported in part by the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health through the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (Z01HG200362).
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alcohol ,blood pressure ,multi-omics ,smoking ,serum lipids ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Genetics ,Molecular Medicine ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,gene-lifestyle interactions ,Genetics (clinical) ,summary data - Abstract
Though both genetic and lifestyle factors are known to influence cardiometabolic outcomes, less attention has been given to whether lifestyle exposures can alter the association between a genetic variant and these outcomes. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium’s Gene-Lifestyle Interactions Working Group has recently published investigations of genome-wide gene-environment interactions in large multi-ancestry meta-analyses with a focus on cigarette smoking and alcohol consumption as lifestyle factors and blood pressure and serum lipids as outcomes. Further description of the biological mechanisms underlying these statistical interactions would represent a significant advance in our understanding of gene-environment interactions, yet accessing and harmonizing individual-level genetic and ‘omics data is challenging. Here, we demonstrate the coordinated use of summary-level data for gene-lifestyle interaction associations on up to 600,000 individuals, differential methylation data, and gene expression data for the characterization and prioritization of loci for future follow-up analyses. Using this approach, we identify 48 genes for which there are multiple sources of functional support for the identified gene-lifestyle interaction. We also identified five genes for which differential expression was observed by the same lifestyle factor for which a gene-lifestyle interaction was found. For instance, in gene-lifestyle interaction analysis, the T allele of rs6490056 (ALDH2) was associated with higher systolic blood pressure, and a larger effect was observed in smokers compared to non-smokers. In gene expression studies, this allele is associated with decreased expression of ALDH2, which is part of a major oxidative pathway. Other results show increased expression of ALDH2 among smokers. Oxidative stress is known to contribute to worsening blood pressure. Together these data support the hypothesis that rs6490056 reduces expression of ALDH2, which raises oxidative stress, leading to an increase in blood pressure, with a stronger effect among smokers, in whom the burden of oxidative stress is greater. Other genes for which the aggregation of data types suggest a potential mechanism include: GCNT4×current smoking (HDL), PTPRZ1×ever-smoking (HDL), SYN2×current smoking (pulse pressure), and TMEM116×ever-smoking (mean arterial pressure). This work demonstrates the utility of careful curation of summary-level data from a variety of sources to prioritize gene-lifestyle interaction loci for follow-up analyses.
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- 2022
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13. Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant
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Robert A. Redd, Matthew Leventhal, Irene M. Ghobrial, Nikhil C. Munshi, Christopher J. Gibson, Jerome Ritz, Amin Nassar, Chip Stewart, Jihye Park, Romanos Sklavenitis-Pistofidis, Marzia Capelletti, Cody J. Boehner, David P. Steensma, Saud H. AlDubayan, Daniel Auclair, Lorenzo Trippa, Muhieddine M. Itani, Benjamin L. Ebert, Kalvis Hornburg, Shaadi Mehr, Mark Bustoros, Robert L. Schlossman, Henry Dumke, Jacob P. Laubach, Adam S. Sperling, Gad Getz, Salomon Manier, Paul G. Richardson, Eliezer M. Van Allen, Tarek H. Mouhieddine, Sabrin Tahri, Kenneth C. Anderson, Robert J. Soiffer, Daisy Huynh, Donna Neuberg, Brendan Reardon, Chia Jen Liu, Jonathan J Keats, Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Department of Hematology [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Brigham and Women's Hospital [Boston], Massachusetts General Hospital [Boston], The Translational Genomics Research Institute (TGen), Multiple Myeloma Research Foundation [Norwalk, CT, États-Unis], Harvard T.H. Chan School of Public Health, We would also like to thank the International Myeloma Society (IMS) for their support. This work was supported by grants from the Multiple Myeloma Research Foundation (MMRF), Adelson Medical Research Foundation (AMRF), Stand Up to Cancer (SU2C) and the Leukemia and Lymphoma Society (LLS) awarded to Dr. Irene M. Ghobrial., Bodescot, Myriam, Lille Neurosciences & Cognition - U 1172 (LilNCog), and Harvard University-Massachusetts Institute of Technology (MIT)
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0301 basic medicine ,Oncology ,Male ,[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Cancer therapy ,medicine.medical_treatment ,General Physics and Astronomy ,Myeloma ,DNA Methyltransferase 3A ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Cancer genomics ,DNA (Cytosine-5-)-Methyltransferases ,lcsh:Science ,Multiple myeloma ,Aged, 80 and over ,Multidisciplinary ,Hematopoietic Stem Cell Transplantation ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Middle Aged ,Progression-Free Survival ,3. Good health ,DNA-Binding Proteins ,Haematopoiesis ,030220 oncology & carcinogenesis ,Female ,Stem cell ,Multiple Myeloma ,Adult ,medicine.medical_specialty ,Science ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Transplantation, Autologous ,General Biochemistry, Genetics and Molecular Biology ,Article ,Dioxygenases ,03 medical and health sciences ,Young Adult ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Internal medicine ,Proto-Oncogene Proteins ,medicine ,Humans ,Progression-free survival ,Aged ,Chemotherapy ,Haematological cancer ,business.industry ,Induction chemotherapy ,Cancer ,General Chemistry ,medicine.disease ,Hematopoiesis ,Transplantation ,030104 developmental biology ,Mutation ,lcsh:Q ,Tumor Suppressor Protein p53 ,business - Abstract
Multiple myeloma (MM) is a plasma-cell neoplasm that is treated with high-dose chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. The presence of somatic mutations in the peripheral blood is termed clonal hematopoiesis of indeterminate potential (CHIP) and is associated with adverse outcomes. Targeted sequencing of the stem cell product from 629 MM patients treated by ASCT at the Dana-Farber Cancer Institute (2003–2011) detects CHIP in 136/629 patients (21.6%). The most commonly mutated genes are DNMT3A, TET2, TP53, ASXL1 and PPM1D. Twenty-one from fifty-six patients (3.3%) receiving first-line IMiD maintenance develop a therapy-related myeloid neoplasm (TMN). However, regardless of CHIP status, the use of IMiD maintenance associates with improved PFS and OS. In those not receiving IMiD maintenance, CHIP is associated with decreased overall survival (OS) (HR:1.34, p = 0.02) and progression free survival (PFS) (HR:1.45, p, Multiple myeloma (MM) is treated with induction chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. Here, the authors show that the presence of clonal haematopoiesis of indeterminate potential (CHIP) at time of ASCT is associated with adverse outcomes in MM patients.
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- 2020
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14. A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery
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Crouchet, Emilie, Bandiera, Simonetta, Fujiwara, Naoto, Li, Shen, El Saghire, Hussein, Fernández-Vaquero, Mirian, Riedl, Tobias, Sun, Xiaochen, Hirschfield, Hadassa, Jühling, Frank, Zhu, Shijia, Roehlen, Natascha, Ponsolles, Clara, Heydmann, Laura, Saviano, Antonio, Qian, Tongqi, Venkatesh, Anu, Lupberger, Joachim, Verrier, Eloi R., Sojoodi, Mozhdeh, Oudot, Marine A., Duong, François H. T., Masia, Ricard, Wei, Lan, Thumann, Christine, Durand, Sarah C., González-Motos, Victor, Heide, Danijela, Hetzer, Jenny, Nakagawa, Shigeki, Ono, Atsushi, Song, Won-Min, Higashi, Takaaki, Sanchez, Roberto, Kim, Rosa S., Bian, C. Billie, Kiani, Karun, Croonenborghs, Tom, Subramanian, Aravind, Chung, Raymond T., Straub, Beate K., Schuppan, Detlef, Ankavay, Maliki, Cocquerel, Laurence, Schaeffer, Evelyne, Goossens, Nicolas, Koh, Anna P., Mahajan, Milind, Nair, Venugopalan D., Gunasekaran, Ganesh, Schwartz, Myron E., Bardeesy, Nabeel, Shalek, Alex K., Rozenblatt-Rosen, Orit, Regev, Aviv, Felli, Emanuele, Pessaux, Patrick, Tanabe, Kenneth K., Heikenwälder, Mathias, Schuster, Catherine, Pochet, Nathalie, Zeisel, Mirjam B., Fuchs, Bryan C., Hoshida, Yujin, Baumert, Thomas F., Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Texas Southwestern Medical Center [Dallas], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Universität Heidelberg [Heidelberg] = Heidelberg University, Nouvel Hôpital Civil de Strasbourg, University Hospital Basel [Basel], Hiroshima University, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Kumamoto University, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), University Medical Center of the Johannes Gutenberg-University Mainz, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Geneva University Hospital (HUG), Massachusetts Institute of Technology (MIT), Harvard University, This work was supported by ARC, Paris and Institut Hospitalo-Universitaire, Strasbourg (TheraHCC1.0 and 2.0 IHUARC IHU201301187 and IHUARC2019 to T.F.B.), the European Union (ERC-AdG-2014-671231-HEPCIR to T.F.B. and Y.H., EU H2020-667273-HEPCAR to T.F.B. and M.H., and INTERREG-IV-Rhin Supérieur-FEDER-Hepato-Regio-Net 2012 to T.F.B. and M.B.Z), ANRS, Paris (2013/108 and ECTZ103701 to T.F.B), NIH (DK099558 to Y. H., and CA233794 to Y.H. and T. F. B, CA140861 to B.C.F., and CA209940, R21CA209940, and R03AI131066 to N.P. and T.F.B.), Cancer Prevention and Research Institute of Texas (RR180016 to Y.H.), US Department of Defense (W81XWH-16-1-0363 to T.F.B. and Y.H.), the Irma T. Hirschl/Monique Weill-Caulier Trust (Y.H.), and the Foundation of the University of Strasbourg (HEPKIN to T. F. B. and Y. H.) and the Institut Universitaire de France (IUF, T.F.B.). M.H. is supported by an ERC CoG grant (HepatoMetaboPath) and EOS grant and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID 272983813—TRR 179, and Project-ID 314905040 SFB TR209. This work has been published under the framework of the LABEX ANR-10-LABX-0028_HEPSYS and Inserm Plan Cancer and benefits from funding from the state managed by the French National Research Agency as part of the Investments for the future program., ANR-10-LABX-0028,HepSys,Functional genomics of viral hepatitis and liver disease(2010), European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016), European Project: 667273,H2020,H2020-PHC-2015-two-stage,HEP-CAR(2016), Cocquerel, Laurence, Functional genomics of viral hepatitis and liver disease - - HepSys2010 - ANR-10-LABX-0028 - LABX - VALID, Cell circuits as targets and biomarkers for liver disease and cancer prevention - HEPCIR - - H20202016-01-01 - 2020-12-31 - 671231 - VALID, Mechanisms underlying hepatocellular carcinoma pathogenesis and impact of co-morbidities. - HEP-CAR - - H20202016-01-01 - 2019-12-31 - 667273 - VALID, Universität Heidelberg [Heidelberg], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Harvard University [Cambridge], Johannes Gutenberg - Universität Mainz (JGU), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
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Liver Cirrhosis ,Male ,Carcinoma, Hepatocellular ,Hepatocellular carcinoma ,Carcinogenesis ,Science ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Hepacivirus ,Sciences du Vivant [q-bio]/Médecine humaine et pathologie ,Chemoprevention ,Models, Biological ,Article ,Cohort Studies ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Cell Line, Tumor ,Drug Discovery ,Cancer genomics ,Cyclic AMP ,Animals ,Humans ,Cyclic AMP Response Element-Binding Protein ,Immunologic Surveillance ,Liver diseases ,Nizatidine ,Inflammation ,Mice, Knockout ,Macrophages ,Liver Neoplasms ,Prognosis ,Hepatitis C ,Computational biology and bioinformatics ,Gene Expression Regulation, Neoplastic ,Disease Models, Animal ,Mechanisms of disease ,HEK293 Cells ,Liver ,Hepatocytes ,Transcriptome ,Signal Transduction - Abstract
Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. Here, we develop a simple and robust human liver cell-based system modeling a clinical prognostic liver signature (PLS) predicting long-term liver disease progression toward HCC. Using the PLS as a readout, followed by validation in nonalcoholic steatohepatitis/fibrosis/HCC animal models and patient-derived liver spheroids, we identify nizatidine, a histamine receptor H2 (HRH2) blocker, for treatment of advanced liver disease and HCC chemoprevention. Moreover, perturbation studies combined with single cell RNA-Seq analyses of patient liver tissues uncover hepatocytes and HRH2+, CLEC5Ahigh, MARCOlow liver macrophages as potential nizatidine targets. The PLS model combined with single cell RNA-Seq of patient tissues enables discovery of urgently needed targets and therapeutics for treatment of advanced liver disease and cancer prevention., Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.
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- 2021
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15. Comparative genomics of white and opaque cell states supports an epigenetic mechanism of phenotypic switching in Candida albicans
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Richard J. Bennett, Iuliana V. Ene, Chapman N. Beekman, Christina A. Cuomo, Brown University, Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), and This work was supported by NIH NIAID R21AI139592 and NIH NIGMS IDeA award (P20GM109035) to I.V.E., and by NIH NIAID R01 AI081704 and R01 AI141893 to R.J.B. C.A.C. was supported by NIH NIAID award U19AI110818 to the Broad Institute.
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AcademicSubjects/SCI01140 ,AcademicSubjects/SCI00010 ,[SDV]Life Sciences [q-bio] ,Phenotypic switching ,comparative genomics ,AcademicSubjects/SCI01180 ,MESH: Phenotype ,Epigenesis, Genetic ,Fungal Proteins ,03 medical and health sciences ,Gene Expression Regulation, Fungal ,Genetic variation ,Gene expression ,Candida albicans ,Genetics ,Gene Regulatory Networks ,Epigenetics ,MESH: Epigenesis, Genetic ,Molecular Biology ,Genetics (clinical) ,030304 developmental biology ,MESH: Gene Regulatory Networks ,Comparative genomics ,0303 health sciences ,epigenetic switch ,biology ,030306 microbiology ,MESH: Candida albicans ,MESH: Genomics ,Genomics ,biology.organism_classification ,Corpus albicans ,Genome Report ,White (mutation) ,Phenotype ,AcademicSubjects/SCI00960 ,MESH: Fungal Proteins ,MESH: Gene Expression Regulation, Fungal - Abstract
Several Candida species can undergo a heritable and reversible transition from a ‘white’ state to a mating proficient ‘opaque’ state. This ability relies on highly interconnected transcriptional networks that control cell-type-specific gene expression programs over multiple generations. Candida albicans, the most prominent pathogenic Candida species, provides a well-studied paradigm for the white-opaque transition. In this species, a network of at least eight transcriptional regulators controls the balance between white and opaque states that have distinct morphologies, transcriptional profiles, and physiological properties. Given the reversible nature and the high frequency of white-opaque transitions, it is widely assumed that this switch is governed by epigenetic mechanisms that occur independently of any changes in DNA sequence. However, a direct genomic comparison between white and opaque cells has yet to be performed. Here, we present a whole-genome comparative analysis of C. albicans white and opaque cells. This analysis revealed rare genetic changes between cell states, none of which are linked to white-opaque switching. This result is consistent with epigenetic mechanisms controlling cell state differentiation in C. albicans and provides direct evidence against a role for genetic variation in mediating the switch.
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- 2021
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16. Genetic correlates of phenotypic heterogeneity in autism
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Warrier, Varun, Zhang, Xinhe, Reed, Patrick, Havdahl, Alexandra, Moore, Tyler M., Cliquet, Freddy, Leblond, Claire S., Rolland, Thomas, Rosengren, Anders, Caceres, Antonia San Jose, Hayward, Hannah, Crawley, Daisy, Faulkner, Jessica, Sabet, Jessica, Ellis, Claire, Oakley, Bethany, Loth, Eva, Charman, Tony, Murphy, Declan, Holt, Rosemary, Waldman, Jack, Upadhyay, Jessica, Gunby, Nicola, Lai, Meng-Chuan, Renouf, Gwilym, Ruigrok, Amber, Taylor, Emily, Ziauddeen, Hisham, Deakin, Julia, di Bruttopilo, Sara Ambrosino, van Dijk, Sarai, Rijks, Yvonne, Koops, Tabitha, Douma, Miriam, Spaan, Alyssia, Selten, Iris, Steffers, Maarten, van Themaat, Anna Ver Loren, Bast, Nico, Baumeister, Sarah, O’Dwyer, Larry, Bours, Carsten, Rausch, Annika, von Rhein, Daniel, Cornelissen, Ineke, de Bruin, Yvette, Graauwmans, Maartje, Kostrzewa, Elzbieta, Cauvet, Elodie, Tammimies, Kristiina, Sitnikow, Rouslan, Dumas, Guillaume, Kim, Yang-Min, Bourgeron, Thomas, Hougaard, David M., Bybjerg-Grauholm, Jonas, Werge, Thomas, Mortensen, Preben Bo, Mors, Ole, Nordentoft, Merete, Adhya, Dwaipayan, Alamanza, Armandina, Allison, Carrie, Garvey, Isabelle, Parsons, Tracey, Smith, Paula, Tsompanidis, Alex, Burton, Graham J., Heazell, Alexander E. P., Gabis, Lidia V., Biron-Shental, Tal, Lancaster, Madeline A., Srivastava, Deepak P., Mill, Jonathan, Rowitch, David H., Hurles, Matthew E., Geschwind, Daniel H., Børglum, Anders D., Robinson, Elise B., Grove, Jakob, Martin, Hilary C., Baron-Cohen, Simon, University of Cambridge [UK] (CAM), Lovisenberg Diakonale Sykehus - Lovisenberg Diaconal Hospital [Oslo], Norwegian Institute of Public Health [Oslo] (NIPH), University of Oslo (UiO), University of Pennsylvania [Philadelphia], Children’s Hospital of Philadelphia (CHOP ), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen University Hospital, The Wellcome Trust Sanger Institute [Cambridge], University of California [Los Angeles] (UCLA), University of California, Aarhus University [Aarhus], Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Massachusetts General Hospital [Boston], Harvard T.H. Chan School of Public Health, V.W. is funded by St. Catharine’s College, Cambridge. This study was funded by grants to SBC from the Medical Research Council, the Wellcome Trust, the Autism Research Trust, the Templeton World Charity Foundation, and to T.B. from the Institut Pasteur, the CNRS, The Bettencourt-Schueller and the Cognacq-Jay Foundations, the APHP and the Université de Paris. SBC was funded by the Autism Research Trust, the Wellcome Trust, the Templeton World Charitable Foundation, and the NIHR Biomedical Research Centre in Cambridge, during the period of this work. The Medical Research Council (MRC) funded the Cambridge Autism Research Database (CARD) that made this study possible. SBC also received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 777394. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. His research was also supported by the National Institute of Health Research (NIHR) Applied Research Collaboration East of England (ARC EoE) programme. T.M.M. is supported by U.S. National Institutes of Mental Health (NIMH) grant MH117014. The views expressed are those of the authors, and not necessarily those of the NIHR, NHS or Department of Health and Social Care. We acknowledge with gratitude the generous support of Drs Dennis and Mireille Gillings in strengthening the collaboration between S.B.-C. and T.B., and between Cambridge University and the Institut Pasteur. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The AIMS-2-TRIALS LEAP receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. A full list of the authors and affiliations in the AIMS-2-TRIALS LEAP group is provided in the Supplementary Information. The iPSYCH team was supported by grants from the Lundbeck Foundation (R102-A9118, R155-2014-1724 and R248-2017-2003), NIMH (1U01MH109514-01 to ADB) and the universities and university hospitals of Aarhus and Copenhagen. The Danish National Biobank resource was supported by the Novo Nordisk Foundation. High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark (grant to ADB). We thank Jonathan Sebat for sharing the de novo variant calls in the SPARK and SSC datasets., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Warrier, Varun [0000-0003-4532-8571], Havdahl, Alexandra [0000-0002-9268-0423], Moore, Tyler M [0000-0002-1384-0151], Rosengren, Anders [0000-0002-6682-1288], Hurles, Matthew E [0000-0002-2333-7015], Geschwind, Daniel H [0000-0003-2896-3450], Børglum, Anders D [0000-0001-8627-7219], Grove, Jakob [0000-0003-2284-5744], Martin, Hilary C [0000-0002-4454-9084], Bourgeron, Thomas [0000-0001-8164-9220], Baron-Cohen, Simon [0000-0001-9217-2544], Apollo - University of Cambridge Repository, University of Pennsylvania, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California (UC), Harvard University-Massachusetts Institute of Technology (MIT), and S.B.-C. received funding from the Wellcome Trust (214322\Z\18\Z). For the purpose of open access, we have applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission. S.B.-C. also received funding from the Autism Centre of Excellence, the SFARI, the Templeton World Charitable Fund, the MRC and the National Institute for Health Research Cambridge Biomedical Research Centre. The research was supported by the National Institute for Health Research Applied Research Collaboration East of England. Any views expressed are those of the author(s) and not necessarily those of the funder. Some of the results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 777394 for the project AIMS-2-TRIALS. This joint undertaking receives support from the European Union’s Horizon 2020 research and innovation program and the EFPIA and Autism Speaks, Autistica and the SFARI. V.W. is funded by St. Catharine’s College, Cambridge. T.B. has received funding from the Institut Pasteur, the CNRS, the Bettencourt–Schueller and the Cognacq–Jay Foundations, the APHP and the Université de Paris Cité. We acknowledge with gratitude the generous support of D. and M. Gillings in strengthening the collaboration between S.B.-C. and T.B. and between Cambridge University and the Institut Pasteur. The iPSYCH team was supported by grants from the Lundbeck Foundation (R102-A9118, R155-2014-1724 and R248-2017-2003), the NIMH (1U01MH109514-01 to A.D.B.) and the universities and university hospitals of Aarhus and Copenhagen. The Danish National Biobank resource was supported by the Novo Nordisk Foundation. High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark (grant to A.D.B.). We thank J. Sebat for sharing the de novo variant calls in the SPARK and SSC datasets. We are grateful to all families at the participating SSC sites as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, Z. Warren and E. Wijsman). We are grateful to all families in the SPARK study, the SPARK clinical sites and SPARK staff.
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Male ,Autism Spectrum Disorder ,CHILDREN ,behavioral disciplines and activities ,Developmental psychology ,Correlation ,03 medical and health sciences ,Nonverbal communication ,AGE ,Cognition ,0302 clinical medicine ,Intellectual Disability ,mental disorders ,Genetics ,medicine ,Humans ,Limited evidence ,GENOME-WIDE ASSOCIATION ,Autistic Disorder ,Association (psychology) ,COMMON ,SPECTRUM DISORDER ,030304 developmental biology ,RISK ,ARCHITECTURE ,0303 health sciences ,IDENTIFICATION ,[SCCO.NEUR]Cognitive science/Neuroscience ,medicine.disease ,Educational attainment ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,DE-NOVO MUTATIONS ,Adaptive behaviour ,Schizophrenia ,Autism ,Female ,SIMONS SIMPLEX COLLECTION ,Psychology ,030217 neurology & neurosurgery - Abstract
Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440, Funder: Templeton World Charity Foundation (Templeton World Charity Foundation, Inc.); doi: https://doi.org/10.13039/501100011730, The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (nmax = 12,893) based on core and associated features of autism, co-occurring developmental disabilities and sex. We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors, but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shape cognition, behavior and co-occurring conditions in autism.
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17. Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure
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Lisa W. Martin, Tuomas O. Kilpeläinen, Xiuqing Guo, Kurt Lohman, Ching-Ti Liu, Jerome I. Rotter, Pirjo Komulainen, Lili Milani, Ilja M. Nolte, Yuri Milaneschi, Andres Metspalu, Yii-Der Ida Chen, Tõnu Esko, Jovia L. Nierenberg, Mika Kähönen, Marjan Ilkov, Dennis O. Mook-Kanamori, Karen Schwander, W. James Gauderman, Hanfei Xu, Vilmundur Gudnason, Alisa K. Manning, Gudny Eiriksdottir, David R. Hillman, Elise Lim, Hugues Aschard, John M. Starr, Michael R. Brown, Alanna C. Morrison, Eric Boerwinkle, Stefan Weiss, Maris Alver, Konstantin Strauch, Thomas Meitinger, Tuomo Rankinen, Timo A. Lakka, Harold Snieder, Stephen S. Rich, Yun Ju Sung, Diana van Heemst, Wanqing Wen, Marcus Dörr, Peter J. van der Most, Terho Lehtimäki, Nora Franceschini, Treva Rice, Amy R. Bentley, Dan E. Arking, Susan Redline, Nienke R. Biermasz, Sarah E. Harris, Melanie Waldenberger, Claude Bouchard, M. Arfan Ikram, Walter Palmas, Lynne E. Wagenknecht, Bruce M. Psaty, Daniel Levy, Cornelia M. van Duijn, Joshua C. Bis, Kelly A. Hall, José Eduardo Krieger, Tanika N. Kelly, Kari E. North, Brigitte Kühnel, Phyllis C. Zee, Melissa A. Richard, Lyle J. Palmer, Till Roenneberg, Alexandre C. Pereira, Yongmei Liu, Andrea R. V. R. Horimoto, Jie Yao, Han Chen, Jiang He, Pamela J. Schreiner, Patricia B. Munroe, Wei Zheng, Charles Kooperberg, Paul S. de Vries, Ana Barac, Rainer Rauramaa, Leo-Pekka Lyytikäinen, James M. Shikany, Brian E. Cade, Christian Gieger, Stephen Sidney, Alan B. Zonderman, Tamar Sofer, Chuan Gao, Thomas W. Winkler, Xiao-Ou Shu, Ian J. Deary, Uwe Völker, RJ Waken, Heming Wang, Myriam Fornage, Brenda W.J.H. Penninx, Gregory P. Wilson, Dina Vojinovic, Robert B. Wallace, Kenneth Rice, Ervin R. Fox, Jeffrey R. O'Connell, Annemarie I. Luik, Traci M. Bartz, Xiaofeng Zhu, Najaf Amin, Nicholette D. Palmer, Sami Heikkinen, Kumaraswamynaidu Chitrala, Raymond Noordam, Jiwon Lee, André G. Uitterlinden, Sutapa Mukherjee, Hans J. Grabe, Mario Sims, Sina A. Gharib, Daniel J. Gottlieb, Dabeeru C. Rao, Annette Peters, Reedik Mägi, Solomon K. Musani, Michele K. Evans, Lenore J. Launer, Harvard Medical School [Boston] (HMS), Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Hallym University, Department of Educational Psychology and Counseling, National Taiwan Normal University (NTNU), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Leiden University Medical Center (LUMC), Universiteit Leiden, This project was supported by the US National Heart, Lung, and Blood Institute (NHLBI) R01HL118305. HW and SR were supported by NHLBI R35HL135818. BEC was supported by NHLBI K01HL135405. ARB was supported by the Intramural Research Program of the National Institutes of Health in the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (1ZIAHG200362). D.v.H. was supported by the European Commission funded project HUMAN (Health-2013-INNOVATION-1-602757). The CHARGE cohorts were supported in part by NHLBI infrastructure grant HL105756. Study-specific acknowledgments can be found in the Supplementary Notes., European Project: 602757,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,HUMAN(2013), Life Course Epidemiology (LCE), Epidemiology, Radiology & Nuclear Medicine, Internal Medicine, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Digital Health, Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Tampere University, Department of Clinical Chemistry, Clinical Medicine, and Department of Clinical Physiology and Nuclear Medicine
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0301 basic medicine ,Mean arterial pressure ,Diastole ,Blood Pressure ,Biology ,3121 Internal medicine ,Genome ,Polymorphism, Single Nucleotide ,Elevated blood ,3124 Neurology and psychiatry ,Article ,Cellular and Molecular Neuroscience ,03 medical and health sciences ,TRPC3 ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,Humans ,Molecular Biology ,Gene ,030304 developmental biology ,Genetics ,0303 health sciences ,[STAT.AP]Statistics [stat]/Applications [stat.AP] ,Short sleep ,Sleep in non-human animals ,Pulse pressure ,Psychiatry and Mental health ,030104 developmental biology ,Blood pressure ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Genetic Loci ,Hypertension ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,3111 Biomedicine ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Sleep ,[STAT.ME]Statistics [stat]/Methodology [stat.ME] ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups using 1 degree of freedom (1df) interaction and 2df joint tests. Primary multi-ancestry analyses in 62,969 individuals in stage 1 identified 3 novel loci that were replicated in an additional 59,296 individuals in stage 2, including rs7955964 (FIGNL2/ANKRD33) showing significant 1df interactions with long sleep duration and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) showing significant 1df interactions with short sleep duration (Pint < 5×10−8). Secondary ancestry-specific two-stage analyses and combined stage 1 and 2 analyses additionally identified 23 novel loci that need external replication, including 3 and 5 loci showing significant 1df interactions with long and short sleep duration, respectively (Pint < 5×10−8). Multiple genes mapped to our 26 novel loci have known functions in sleep-wake regulation, nervous and cardiometabolic systems. We also identified new gene by long sleep interactions near five known BP loci (≤1Mb) including NME7, FAM208A, MKLN1, CEP164, and RGL3/ELAVL3 (Pint < 5×10−8). This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
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18. A genome-wide gain-of-function screen identifies CDKN2C as a HBV host factor
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Eller, Carla, Heydmann, Laura, Colpitts, Che C., El Saghire, Houssein, Piccioni, Federica, Jühling, Frank, Majzoub, Karim, Pons, Caroline, Bach, Charlotte, Lucifora, Julie, Lupberger, Joachim, Nassal, Michael, Cowley, Glenn S., Fujiwara, Naoto, Hsieh, Sen-Yung, Hoshida, Yujin, Felli, Emanuele, Pessaux, Patrick, Sureau, Camille, Schuster, Catherine, Root, David E., Verrier, Eloi R., Baumert, Thomas F., Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Queen's University [Kingston, Canada], Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Hospital Freiburg, University of Texas Southwestern Medical Center, Chang Gung Memorial Hospital [Taipei] (CGMH), Pôle Hépato-digestif [Strasbourg], Nouvel Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, Laboratoire de Virologie Moléculaire [Paris], Institut National de la Transfusion Sanguine [Paris] (INTS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), This work was supported by Inserm, the University of Strasbourg, the European Union (ERC-2014-AdG-671231-HEPCIR, Infect-ERA hepBccc, EU H2020 Hep-CAR 667273), the IHU Fondation ARC (French Cancer Agency) TheraHCC program IHU201301187 and IHU201901299, the Institut Universitaire de France and the Agence Nationale de Recherche sur le Sida et les hépatites virales (ANRS) and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R03AI131066. C.C.C. acknowledges fellowships from the Canadian Institutes of Health Research (201411MFE-338606-245517) and the Canadian Network on Hepatitis C. E.R.V. acknowledges fellowship from ANRS (ECTZ50121)., European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016), European Project: 321529,EC:FP7:HEALTH,FP7-ERANET-2012-RTD,INFECT-ERA(2013), European Project: 667273,H2020,H2020-PHC-2015-two-stage,HEP-CAR(2016), Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Bodescot, Myriam, Cell circuits as targets and biomarkers for liver disease and cancer prevention - HEPCIR - - H20202016-01-01 - 2020-12-31 - 671231 - VALID, Coordination of European funding for infectious diseases research - INFECT-ERA - - EC:FP7:HEALTH2013-01-01 - 2016-12-31 - 321529 - VALID, and Mechanisms underlying hepatocellular carcinoma pathogenesis and impact of co-morbidities. - HEP-CAR - - H20202016-01-01 - 2019-12-31 - 667273 - VALID
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Hepatitis B virus ,Science ,Kaplan-Meier Estimate ,[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Virus Replication ,Article ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Cell Line, Tumor ,Cyclin-Dependent Kinase Inhibitor p18 ,Humans ,Genetic Testing ,Viral hepatitis ,lcsh:Science ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Host Microbial Interactions ,Gene Expression Profiling ,virus diseases ,Functional genomics ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Hep G2 Cells ,Hepatitis B ,digestive system diseases ,HEK293 Cells ,Liver ,Gain of Function Mutation ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,lcsh:Q ,RNA Interference ,Genome-Wide Association Study - Abstract
Chronic HBV infection is a major cause of liver disease and cancer worldwide. Approaches for cure are lacking, and the knowledge of virus-host interactions is still limited. Here, we perform a genome-wide gain-of-function screen using a poorly permissive hepatoma cell line to uncover host factors enhancing HBV infection. Validation studies in primary human hepatocytes identified CDKN2C as an important host factor for HBV replication. CDKN2C is overexpressed in highly permissive cells and HBV-infected patients. Mechanistic studies show a role for CDKN2C in inducing cell cycle G1 arrest through inhibition of CDK4/6 associated with the upregulation of HBV transcription enhancers. A correlation between CDKN2C expression and disease progression in HBV-infected patients suggests a role in HBV-induced liver disease. Taken together, we identify a previously undiscovered clinically relevant HBV host factor, allowing the development of improved infectious model systems for drug discovery and the study of the HBV life cycle., Here the authors perform a gain-of-function screen and identify CDKN2C as a host factor for HBV replication, inducing cell cycle arrest and expression of HBV transcription enhancers. CDKN2C expression correlates with disease progression suggesting a potential role in HBV-induced liver disease.
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19. Chemoinformatics approaches to help antibacterial discovery
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Bellanger, Clément, Hung, Jane, Juniarta, Nyoman, Leroux, Vincent, Maigret, Bernard, Napoli, Amedeo, Knowledge representation, reasonning (ORPAILLEUR), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Computational Algorithms for Protein Structures and Interactions (CAPSID), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Harvard University-Massachusetts Institute of Technology (MIT), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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[INFO]Computer Science [cs] ,[CHIM.CHEM]Chemical Sciences/Cheminformatics - Abstract
Many bacteria are acquiring more resistance to usual treatments worldwide, to the point that the possible advent of pathogens resistant to the entire current arsenal is a true concern. Therefore, there is an urgent need for finding new effective antibacterial drugs. Associated to data mining methods, in silico ligand-based drug design techniques may extract the most relevant molecular features and eventually lead to the discovery of innovative potent antibacterial molecules. In this work, we use feature selection techniques to build molecular filters with demonstrated ability to discriminate between antibacterial and non-antibacterial small molecules. A very large number of molecular properties translated into molecular descrip-tors, being simultaneously diverse and redundant, were processed using various feature selection techniques. It is shown that this approach was efficient in decreasing the models complexity by identifying most relevant features for antibac-terial activity. For reducing the number of considered descriptors, we have trained multiple machine learning algorithms until resulting models performance in virtual screening could not be optimized further. We also discuss the interest of using log-linear analysis to improve our data-driven process and to increase the chance to predict efficiently new antibacterials.
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20. Tracing the Evolutionary History and Global Expansion of Candida auris Using Population Genomic Analyses
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Ana Belén Araúz, Elizabeth L. Berkow, Oliver Kurzai, Christopher H. Heath, Rodney Adam, Sahar Althawadi, Xiao Li, Shawn R. Lockhart, Patricia Escandón, Ronen Ben-Ami, Anastasia P. Litvintseva, Lalitha Gade, Alexandre Alanio, Revathi Gunturu, Kaitlin Forsberg, Ana Alastruey-Izquierdo, Nancy A. Chow, Christina A. Cuomo, Amrita Bharat, Marie Desnos-Ollivier, Dianne Gardam, Belinda Calvo, Ronny Martin, José F. Muñoz, Rory M. Welsh, Centers for Disease Control and Prevention (CDC), Broad Institute [Cambridge], Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], Aga Khan University Hospital (AKUH), Nairobi, Mycologie moléculaire - Molecular Mycology, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris], Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), Instituto de Salud Carlos III [Madrid] (ISC), King Faisal Specialist Hospital and Research Centre, Riyadh, Hospital Santo Tomás, Tel Aviv Sourasky Medical Center [Te Aviv], Tel Aviv University [Tel Aviv], Public Health Agency of Canada (PHAC), Universidad del Zulia (LUZ), Instituto Nacional de Salud [Bogota], Fiona Stanley Hospital [Murdoch], Royal Perth Hospital, The University of Western Australia (UWA), Leibniz Institute for Natural Product Research and Infection Biology (Hans Knoell Institute), University of Würzburg = Universität Würzburg, This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under award U19AI110818 to the Broad Institute. C.A.C. is a CIFAR fellow in the Fungal Kingdom Program. This work was also made possible through support from the Advanced Molecular Detection (AMD) initiative at CDC., National Institute of Allergy and Infectious Diseases (United States), Harvard University-Massachusetts Institute of Technology (MIT), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Université Paris Cité (UPCité), King Faisal Specialist Hospital and Research Centre (KFSH & RC), and Tel Aviv University (TAU)
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Azoles ,Antifungal Agents ,Population genetics ,Emerging species ,Echinocandins ,MESH: Azoles ,Molecular clock ,Clade ,MESH: Phylogeny ,Fluconazole ,Phylogeny ,[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology ,Candida ,genome analysis ,emerging species ,0303 health sciences ,education.field_of_study ,Molecular Epidemiology ,Candida auris ,antifungal resistance ,Biological Evolution ,QR1-502 ,3. Good health ,Phylogeography ,MESH: Phylogeography ,MESH: Genome, Fungal ,MESH: Fluconazole ,Genome, Fungal ,MESH: Metagenomics ,MESH: Whole Genome Sequencing ,Research Article ,MESH: Mutation ,Population ,Genes, Fungal ,MESH: Genetics, Population ,Context (language use) ,MESH: Biological Evolution ,Ecological and Evolutionary Science ,Biology ,Microbiology ,MESH: Drug Resistance, Fungal ,03 medical and health sciences ,Phylogenetics ,Drug Resistance, Fungal ,MESH: Candida ,Virology ,Humans ,MESH: Molecular Epidemiology ,Candidiasis, Invasive ,education ,030304 developmental biology ,MESH: Humans ,Molecular epidemiology ,Whole Genome Sequencing ,030306 microbiology ,MESH: Echinocandins ,population genetics ,Antifungal resistance ,Genome analysis ,MESH: Antifungal Agents ,MESH: Candidiasis, Invasive ,Genetics, Population ,Evolutionary biology ,Mutation ,Metagenomics ,MESH: Genes, Fungal - Abstract
In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology., Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris.
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- 2020
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21. Steroid resistance in Diamond Blackfan anemia associates with p57Kip2 dysregulation in erythroid progenitors
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Julien Papoin, Brian M. Dulmovits, Jeffrey M. Lipton, Hongxia Yan, Narla Mohandas, Nan Wang, Christopher D. Hillyer, Steven A. Carr, Lydie Da Costa, Ryan Ashley, Meagan E. Olive, Naomi Taylor, Adrianna Vlachos, Sandrina Kinet, Namrata D. Udeshi, Lionel Blanc, Anupama Narla, John Hale, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Cornell University [New York], Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), The Broad Institute [Cambridge, MA, USA], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), and The Feinstein Institute for Medical Research
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Population ,Drug Resistance ,Context (language use) ,Biology ,Dexamethasone ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Antigens, CD ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Progenitor cell ,Diamond–Blackfan anemia ,education ,Cyclin-Dependent Kinase Inhibitor p57 ,ComputingMilieux_MISCELLANEOUS ,Anemia, Diamond-Blackfan ,Erythroid Precursor Cells ,education.field_of_study ,Hematology ,General Medicine ,medicine.disease ,Up-Regulation ,3. Good health ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Erythropoiesis ,Female ,Cyclin-Dependent Kinase Inhibitor p27 ,Research Article ,medicine.drug - Abstract
Despite the effective clinical use of steroids for the treatment of Diamond Blackfan anemia (DBA), the mechanisms through which glucocorticoids regulate human erythropoiesis remain poorly understood. We report that the sensitivity of erythroid differentiation to dexamethasone is dependent on the developmental origin of human CD34(+) progenitor cells, specifically increasing the expansion of CD34(+) progenitors from peripheral blood (PB) but not cord blood (CB). Dexamethasone treatment of erythroid-differentiated PB, but not CB, CD34(+) progenitors resulted in the expansion of a newly defined CD34(+)CD36(+)CD71(hi)CD105(med) immature colony-forming unit–erythroid (CFU-E) population. Furthermore, proteomics analyses revealed the induction of distinct proteins in dexamethasone-treated PB and CB erythroid progenitors. Dexamethasone treatment of PB progenitors resulted in the specific upregulation of p57(Kip2), a Cip/Kip cyclin–dependent kinase inhibitor, and we identified this induction as critical; shRNA-mediated downregulation of p57(Kip2), but not the related p27(Kip1), significantly attenuated the impact of dexamethasone on erythroid differentiation and inhibited the expansion of the immature CFU-E subset. Notably, in the context of DBA, we found that steroid resistance was associated with dysregulated p57(Kip2) expression. Altogether, these data identify a unique glucocorticoid-responsive human erythroid progenitor and provide new insights into glucocorticoid-based therapeutic strategies for the treatment of patients with DBA.
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- 2020
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22. Genomic architecture and introgression shape a butterfly radiation
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Marcus R. Kronforst, Daniel E. Neafsey, Gilson R. P. Moreira, Brian A. Counterman, W. Owen McMillan, David B. Jaffe, John W. Davey, Michael Miyagi, Bernardo J. Clavijo, Gonzalo García-Accinelli, Nathaniel B. Edelman, Andrew J. Blumberg, Riccardo Papa, Robert D. Reed, Mark Blaxter, Steven M. Van Belleghem, Camilo Salazar, James Mallet, Richard Challis, Federica Di Palma, Paul B. Frandsen, Nick Patterson, Kanchon K. Dasmahapatra, Sujai Kumar, Mathieu Chouteau, Chris D. Jiggins, Mathieu Joron, Rebecca B. Dikow, John Wakeley, The Genome Analysis Centre (TGAC), Smithsonian Institution, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Laboratoire Ecologie, Evolution, Interactions des Systèmes amazoniens (LEEISA), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Guyane (UG)-Centre National de la Recherche Scientifique (CNRS), Institute of Evolutionary Biology, Invasive Species Branch, United States Geological Survey (USGS), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Harvard University, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Department of Organismic and Evolutionary Biology [Cambridge] (OEB), ANR-18-CE02-0019,Supergene,Les conséquences de l'évolution d'un supergène(2018), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Harvard University [Cambridge], Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], Norwich Research Park, Laboratoire Ecologie, évolution, interactions des systèmes amazoniens (LEEISA), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Paul-Valéry - Montpellier 3 (UM3), and Université Paul-Valéry - Montpellier 3 (UM3)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)
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0106 biological sciences ,Introgression ,[SDV]Life Sciences [q-bio] ,Genome, Insect ,Genes, Insect ,Genome ,Gene ,01 natural sciences ,Coalescent theory ,Gene flow ,Adaptive radiation ,Heliconius ,Wings, Animal ,Phylogeny ,Allele ,0303 health sciences ,Multidisciplinary ,Gene rearrangement ,[SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] ,Papilionoidea ,Genomics ,Biological Evolution ,Phylogenetics ,Incompatibility ,Butterflies ,Gene Flow ,Genetic Speciation ,Locus (genetics) ,[SDV.BID]Life Sciences [q-bio]/Biodiversity ,Speciation (biology) ,Biology ,Genetic Introgression ,010603 evolutionary biology ,Article ,03 medical and health sciences ,Gene density ,Animals ,030304 developmental biology ,Butterfly ,Nonhuman ,biology.organism_classification ,Species differentiation ,Evolutionary biology ,Chromosome Inversion - Abstract
We here pioneer a low-cost assembly strategy for 20 Heliconiini genomes to characterize the evolutionary history of the rapidly radiating genusHeliconius. A bifurcating tree provides a poor fit to the data, and we therefore explore a reticulate phylogeny forHeliconius. We probe the genomic architecture of gene flow, and develop a new method to distinguish incomplete lineage sorting from introgression. We find that most loci with non-canonical histories arose through introgression, and are strongly underrepresented in regions of low recombination and high gene density. This is expected if introgressed alleles are more likely to be purged in such regions due to tighter linkage with incompatibility loci. Finally, we identify a hitherto unrecognized inversion, and show it is a convergent structural rearrangement that captures a known color pattern switch locus within the genus. Our multi-genome assembly approach enables an improved understanding of adaptive radiation.
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- 2019
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23. In Silico Karyotyping of Chromosomally Polymorphic Malaria Mosquitoes in the Anopheles gambiae Complex
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Love, R. Rebecca, Redmond, Seth, Pombi, Marco, Caputo, Beniamino, Petrarca, Vincenzo, Della Torre, Alessandra, Anopheles gambiae 1000 Genomes Consortium (including MC Fontaine), The, Besansky, Nora, University of Notre Dame [Indiana] (UND), Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Department of Public Health and Infectious Diseases, Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], and This work was supported by the National Institutes of Health (R01 AI125360 awarded to NJB). During this work, NJB was supported by Target Malaria, which receives core funding from the Bill & Melinda Gates Foundation and from the Open Philanthropy Project Fund, an advised fund of Silicon Valley Community Foundation.
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single nucleotide ,0106 biological sciences ,genotype ,Anopheles gambiae ,chromosomal inversion polymorphism ,QH426-470 ,01 natural sciences ,Genome ,polymorphism ,malaria vector ,inversion genotyping ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Genotype ,karyotype analysis ,humans ,Genetics (clinical) ,Chromosomal inversion ,Genetics ,0303 health sciences ,education.field_of_study ,[SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] ,karyotyping ,Tag SNP ,3. Good health ,animals ,chromosome inversion ,tag SNP ,chromosomes ,Population ,malaria ,Single-nucleotide polymorphism ,Biology ,mosquito vectors ,010603 evolutionary biology ,03 medical and health sciences ,evolution ,genomics ,molecular ,education ,Molecular Biology ,Genotyping ,030304 developmental biology ,biology.organism_classification ,genetic variation ,anopheles gambiae ,tag snp ,anopheles ,evolution, molecular ,polymorphism, single nucleotide ,reproducibility of results ,chromosomes, insect ,polymorphism, genetic ,insect ,genetic ,[SDE.BE]Environmental Sciences/Biodiversity and Ecology - Abstract
Chromosomal inversion polymorphisms play an important role in adaptation to environmental heterogeneities. For mosquito species in the Anopheles gambiae complex that are significant vectors of human malaria, paracentric inversion polymorphisms are abundant and are associated with ecologically and epidemiologically important phenotypes. Improved understanding of these traits relies on determining mosquito karyotype, which currently depends upon laborious cytogenetic methods whose application is limited both by the requirement for specialized expertise and for properly preserved adult females at specific gonotrophic stages. To overcome this limitation, we developed sets of tag single nucleotide polymorphisms (SNPs) inside inversions whose biallelic genotype is strongly correlated with inversion genotype. We leveraged 1,347 fully sequenced An. gambiae and Anopheles coluzzii genomes in the Ag1000G database of natural variation. Beginning with principal components analysis (PCA) of population samples, applied to windows of the genome containing individual chromosomal rearrangements, we classified samples into three inversion genotypes, distinguishing homozygous inverted and homozygous uninverted groups by inclusion of the small subset of specimens in Ag1000G that are associated with cytogenetic metadata. We then assessed the correlation between candidate tag SNP genotypes and PCA-based inversion genotypes in our training sets, selecting those candidates with >80% agreement. Our initial tests both in held-back validation samples from Ag1000G and in data independent of Ag1000G suggest that when used for in silico inversion genotyping of sequenced mosquitoes, these tags perform better than traditional cytogenetics, even for specimens where only a small subset of the tag SNPs can be successfully ascertained.
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24. Combined Analysis of Metabolomes, Proteomes, and Transcriptomes of Hepatitis C Virus–Infected Cells and Liver to Identify Pathways Associated With Disease Development
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Ralf Bartenschlager, Kazuaki Chayama, Joachim Lupberger, Nabeel Bardeesy, Eloi R. Verrier, Nicolaas Van Renne, Tom Croonenborghs, Philipp Mertins, Armando Andres Roca Suarez, Steven A. Carr, Frank Jühling, Yujin Hoshida, Evelyn Ramberger, Mirjam B. Zeisel, Olivier Gevaert, Nourdine Hamdane, Marine A. Oudot, Gergö Meszaros, Alessia Virzì, Mohsen Nabian, Thomas F. Baumert, Daniel Brumaru, Romeo Ricci, Rileen Sinha, Naoto Fujiwara, Hussein El Saghire, Simonetta Bandiera, Marko Jovanovic, Carole Jamey, Celine Everaert, Shaunt Fereshetian, Nathalie Pochet, Laura Heydmann, Sarah C. Durand, Nassim Dali-Youcef, Atish Mukherji, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Harvard-MIT Division of Health Sciences and Technology [Cambridge], Massachusetts Institute of Technology (MIT), Evergrande Center for Immunologic Diseases [Boston, MA, USA] (Ann Romney Center for Neurologic Diseases), Brigham & Women's Hospital, Harvard Medical School, Université de Strasbourg (UNISTRA), Laboratoire de Biochimie et de Biologie Moléculaire, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Department of Infectious Diseases [Heidelberg, Germany], Heidelberg University Hospital [Heidelberg], Division of Virus-Associated Carcinogenesis [Heidelberg, Germany], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), The Broad Institute [Cambridge, MA, USA], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Proteomics Platform [Berlin, Germany], Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz Society [Berlin, Germany], Institute of Public Health [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Hiroshima University, Liver Research Project Center [Hiroshima, Japan], Massachusetts General Hospital [Boston], Harold C. Simmons Comprehensive Cancer Center [Dallas, TX, États-Unis], University of Texas Southwestern Medical Center [Dallas], Cell Circuits Program [Cambridge, MA, USA], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Stanford Center for BioMedical Informatics Research (BMIR), Stanford University, Department of Neurology [Cambridge, MA, USA] (Ann Romney Center for Neurologic Diseases), Harvard Medical School [Boston] (HMS)-Brigham and Women's Hospital [Boston], Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Pôle hépato-digestif [Strasbourg], Nouvel Hôpital Civil, Hospices Civils de Strasbourg-Institut Hospitalo-Universitaire de strasbourg, This work was supported by the European Union (ERC-AdG-2014 HEPCIR to Thomas F. Baumert and Yujin Hoshida and EU H2020 HEPCAR 667273 to Thomas F. Baumert and Joachim Lupberger), the Agence nationale de recherche sur le sida et les hépatites virales (ECTZ4236 to Joachim Lupberger and ECTZ4446 to Armando Andres Roca Suarez), the French Cancer Agency (ARC IHU201301187 to Thomas F. Baumert), the US Department of Defense (W81XWH-16-1-0363 to Thomas F. Baumert and Yujin Hoshida), the National Institutes of Health (National Institute of Allergy and Infectious Diseases R03AI131066 to Nathalie Pochet and Thomas F. Baumert, National Cancer Institute 1R21CA209940 to Nathalie Pochet, Thomas F. Baumert, and Olivier Gevaert, National Institute of Allergy and Infectious Diseases 5U19AI123862-02 to Thomas F. Baumert, National Cancer Institute/Informatics Technology for Cancer Research (ITCR) U01 CA214846 to Nathalie Pochet and Olivier Gevaert), the Fondation de l’Université de Strasbourg (HEPKIN) (TBA-DON-0002) and the INSERM Plan Cancer 2019-2023 to Thomas F. Baumert. This work has benefitted from support by the Initiative of Excellence IDEX-Unistra (ANR-10-IDEX-0002-02 to Joachim Lupberger) and has been published under the framework of the LABEX ANR-10-LAB-28 (HEPSYS). INSERM Plan Cancer, IDEX, and LABEX are initiatives from the French program 'Investments for the Future.' The work of Ralf Bartenschlager was supported by the Deutsche Forschungsgemeinschaft (TRR179, TP9). Kazuaki Chayama was supported by the Research Program on Hepatitis from the Japanese Agency for Medical Research and Development (AMED) Japan (JP18fk0210020h0002). The work of Romeo Ricci and Gergö Meszaros was supported by a European Research Council (ERC) starting grant (ERC-2011-StG, 281271-STRESS METABOL), by the European Foundation for the Study of Diabetes (EFSD)/Lilly European Diabetes Research Program grant, and by the ANR-10-LABX-0030-INRT grant, a French State fund managed by the ANR under the frame program Investissements d’Avenir ANR-10-IDEX0002-02., daulny, anne, and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Proteomics ,Cirrhosis ,Peroxisome proliferator-activated receptor ,Datasets as Topic ,Hepacivirus ,medicine.disease_cause ,Sciences du Vivant [q-bio]/Cancer ,Transcriptome ,Liver disease ,Mice ,0302 clinical medicine ,Sciences du Vivant [q-bio]/Immunologie ,HCC ,chemistry.chemical_classification ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Fatty liver ,Gastroenterology ,Sciences du Vivant [q-bio]/Biotechnologies ,metabolic disease ,3. Good health ,Liver ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,signal transduction ,STAT3 Transcription Factor ,Hepatitis C virus ,Biology ,Sciences du Vivant [q-bio]/Médecine humaine et pathologie ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Peroxisomes ,Animals ,Humans ,Metabolomics ,Transplantation Chimera ,Hepatology ,Gene Expression Profiling ,immune regulation ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Hepatitis C, Chronic ,medicine.disease ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,digestive system diseases ,Disease Models, Animal ,030104 developmental biology ,Glucose ,chemistry ,Cancer research ,Hepatocytes ,Steatohepatitis ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Comment inMulti-omic Analyses Reveal Complex Interactions Between HCV and Hepatocytes Demonstrating That the Red Queen Is Up and Running. [Gastroenterology. 2019]; International audience; BACKGROUND & AIMS:The mechanisms of hepatitis C virus (HCV) infection, liver disease progression, and hepatocarcinogenesis are only partially understood. We performed genomic, proteomic, and metabolomic analyses of HCV-infected cells and chimeric mice to learn more about these processes.METHODS:Huh7.5.1dif (hepatocyte-like cells) were infected with culture-derived HCV and used in RNA sequencing, proteomic, metabolomic, and integrative genomic analyses. uPA/SCID (urokinase-type plasminogen activator/severe combined immunodeficiency) mice were injected with serum from HCV-infected patients; 8 weeks later, liver tissues were collected and analyzed by RNA sequencing and proteomics. Using differential expression, gene set enrichment analyses, and protein interaction mapping, we identified pathways that changed in response to HCV infection. We validated our findings in studies of liver tissues from 216 patients with HCV infection and early-stage cirrhosis and paired biopsy specimens from 99 patients with hepatocellular carcinoma, including 17 patients with histologic features of steatohepatitis. Cirrhotic liver tissues from patients with HCV infection were classified into 2 groups based on relative peroxisome function; outcomes assessed included Child-Pugh class, development of hepatocellular carcinoma, survival, and steatohepatitis. Hepatocellular carcinomas were classified according to steatohepatitis; the outcome was relative peroxisomal function.RESULTS:We quantified 21,950 messenger RNAs (mRNAs) and 8297 proteins in HCV-infected cells. Upon HCV infection of hepatocyte-like cells and chimeric mice, we observed significant changes in levels of mRNAs and proteins involved in metabolism and hepatocarcinogenesis. HCV infection of hepatocyte-like cells significantly increased levels of the mRNAs, but not proteins, that regulate the innate immune response; we believe this was due to the inhibition of translation in these cells. HCV infection of hepatocyte-like cells increased glucose consumption and metabolism and the STAT3 signaling pathway and reduced peroxisome function. Peroxisomes mediate β-oxidation of very long-chain fatty acids; we found intracellular accumulation of very long-chain fatty acids in HCV-infected cells, which is also observed in patients with fatty liver disease. Cells in livers from HCV-infected mice had significant reductions in levels of the mRNAs and proteins associated with peroxisome function, indicating perturbation of peroxisomes. We found that defects in peroxisome function were associated with outcomes and features of HCV-associated cirrhosis, fatty liver disease, and hepatocellular carcinoma in patients.CONCLUSIONS:We performed combined transcriptome, proteome, and metabolome analyses of liver tissues from HCV-infected hepatocyte-like cells and HCV-infected mice. We found that HCV infection increases glucose metabolism and the STAT3 signaling pathway and thereby reduces peroxisome function; alterations in the expression levels of peroxisome genes were associated with outcomes of patients with liver diseases. These findings provide insights into liver disease pathogenesis and might be used to identify new therapeutic targets.
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25. Recessive gene disruptions in autism spectrum disorder
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Doan, R. N., Lim, E. T., De Rubeis, S., Betancur, C., Cutler, D. J., Chiocchetti, A. G., Overman, L. M., Soucy, A., Goetze, S., Asc, Consortium, Brusco, A., Curró, A., Fallerini, C., Lopergolo, D., Lintas, C., Domenici, E., Dalla Bernardina, B., Ferrero, G. B., Giorgio, E., Trabetti, E., Renieri, A., Riberi, E., Freitag, C. M., Daly, M. J., Walsh, C. A., Buxbaum, J. D., T. W., Yu, Dupuis, Christine, Boston Children's Hospital, Harvard Medical School [Boston] (HMS), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Emory University School of Medicine, Emory University [Atlanta, GA], Universitätsklinikum Frankfurt, Goethe-University Frankfurt am Main, Newcastle University [Newcastle], Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Massachusetts General Hospital [Boston], Howard Hughes Medical Institute [Boston] (HHMI), Howard Hughes Medical Institute (HHMI)-Harvard Medical School [Boston] (HMS), Autism Sequencing Consortium, Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Génétique de l'autisme = Genetics of Autism (NPS-01), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge]
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Male ,genetic structures ,Autism Spectrum Disorder ,[SDV]Life Sciences [q-bio] ,Allelic Imbalance ,medicine.disease_cause ,Whole Exome Sequencing ,Cohort Studies ,0302 clinical medicine ,Missense mutation ,MESH: Cohort Studies ,Exome sequencing ,MESH: Autism Spectrum Disorder ,Genetics ,0303 health sciences ,Mutation ,Genome ,biology ,SLC1A1 ,MESH: Genetic Predisposition to Disease ,MESH: Case-Control Studies ,[SDV] Life Sciences [q-bio] ,Case-Control Studies ,Female ,Genes, Recessive ,Genome, Human ,Humans ,Genetic Predisposition to Disease ,Mutation, Missense ,Autism spectrum disorder ,Human ,Article ,03 medical and health sciences ,MESH: Whole Exome Sequencing ,mental disorders ,Exome Sequencing ,medicine ,Recessive ,Gene ,MESH: Genes, Recessive ,MESH: Genome, Human ,030304 developmental biology ,MESH: Mutation, Missense ,MESH: Humans ,MESH: Allelic Imbalance ,Case-control study ,medicine.disease ,MESH: Male ,Genes ,biology.protein ,Missense ,MESH: Female ,030217 neurology & neurosurgery - Abstract
Autism spectrum disorder (ASD) affects up to 1 in 59 individuals1. Genome-wide association and large-scale sequencing studies strongly implicate both common variants2–4 and rare de novo variants5–10 in ASD. Recessive mutations have also been implicated11–14 but their contribution remains less well defined. Here we demonstrate an excess of biallelic loss-of-function and damaging missense mutations in a large ASD cohort, corresponding to ~5% of total cases, including 10% of females, consistent with a female protective effect. We document biallelic disruption of known or emerging recessive neurodevelopmental genes (CA2, DDHD1, NSUN2, PAH, RARB, ROGDI, SLC1A1, USH2A) as well as other genes not previously implicated in ASD including the transcription factor FEV, a key regulator of the serotonergic circuitry. Our data refine estimates of the contribution of recessive mutation to ASD and suggest new paths for illuminating novel biological pathways responsible for this condition., Editorial Summary: Analysis of whole exome sequencing data from 2,343 individuals with autism spectrum disorder (ASD) compared to 5,852 unaffected individuals demonstrates an excess of biallelic, autosomal mutations for both loss-of-function and damaging missense variants.
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- 2018
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26. Novel genetic loci associated with hippocampal volume
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Benjamin S. Aribisala, Marjolein M.J. van Donkelaar, Randy L. Gollub, Rachel M. Brouwer, Norman Delanty, Tomas Axelsson, Oscar L. Lopez, Thomas Espeseth, Alejandro Arias-Vasquez, Kristel R. van Eijk, Tien Yin Wong, Jeroen van der Grond, Georg Homuth, James T. Becker, Sebastian Guelfi, Anton J. M. de Craen, Bruno Vellas, Christopher R.K. Ching, Charles C. DeCarli, Janita Bralten, Lars T. Westlye, Ryota Hashimoto, Sampath Arepalli, Bertram Müller-Myhsok, Loes M. Olde Loohuis, Sudha Seshadri, Simon E. Fisher, K Hegenscheid, Konstantinos Arfanakis, Zdenka Pausova, Robert C. Green, Simone Reppermund, Katie L. McMahon, Ashley Beecham, Daan van Rooij, Marcel P. Zwiers, Karen A. Mather, Randy L. Buckner, Edith Hofer, Marcella Rietschel, Fabrice Crivello, Ronald H. Zielke, G. Bruce Pike, Thomas W. Mühleisen, Myriam Fornage, Kazutaka Ohi, Gareth E. Davies, Chantal Depondt, Gabriel Cuellar-Partida, Iryna O. Fedko, Peter R. Schofield, Steven G. Potkin, Albert Hofman, Paul M. Thompson, Wiro J. Niessen, Deborah Janowitz, Nicholas G. Martin, Li Shen, Mina Ryten, Meike W. Vernooij, Michael E. Weale, Tonya White, Dennis van 't Ent, Sudheer Giddaluru, Nanda Rommelse, Wei Wen, Sven J. van der Lee, Eco J. C. de Geus, Aaron Goldman, Joanne E. Curran, Qiang Chen, Jean Shin, Wayne C. Drevets, Thomas H. Mosley, Matthias Nauck, Massimo Pandolfo, Anders M. Dale, Paul A. Nyquist, Girma Woldehawariat, Francis J. McMahon, Najaf Amin, Emma J. Rose, Norbert Hosten, David J. Stott, Sigurdur Sigursson, Andrew J. Saykin, M. Kamran Ikram, Pieter J. Hoekstra, Neda Jahanshad, Grant W. Montgomery, Michael Weiner, Aad van der Lugt, Esther Walton, Gunter Schumann, Clyde Francks, Narelle K. Hansell, Xinmin Liu, Herve Lemaitre, Cornelia M. van Duijn, Ralph L. Sacco, Clinton B. Wright, Arvin Saremi, Clifford R. Jack, Andre G. Uitterlinden, G. Donohoe, Tomáš Paus, Michael Griswold, Peter T. Fox, Alan B. Zonderman, Lukas Pirpamer, Christiane Wolf, Aiden Corvin, Shannon L. Risacher, Ian Ford, Philippe Amouyel, Henrik Walter, Beng-Choon Ho, William T. Longstreth, M. Arfan Ikram, Hieab H.H. Adams, Colin Smith, Sungeun Kim, Simon Lovestone, Stefan Ehrlich, Benno Pütz, Markus M. Nöthen, Susana Muñoz Maniega, Ian J. Deary, Elena Shumskaya, Susan H. Blanton, Jerome I. Rotter, Neeltje E.M. van Haren, Mar Matarin, I. Kloszewska, Ganesh Chauhan, Anita L. DeStefano, Barbara Franke, Lars Nyberg, Tatiana Foroud, Tianye Jia, Manon Bernard, Unn K. Haukvik, Rebecca F. Gottesman, Srdjan Djurovic, Ching-Yu Cheng, Lachlan T. Strike, Alex P. Zijdenbos, Jouke-Jan Hottenga, Vince D. Calhoun, Yuri Milaneschi, David C. Glahn, Phil Lee, Amelia A. Assareh, Adaikalavan Ramasamy, Emma Sprooten, Debra A. Fleischman, David R. McKay, J. Raphael Gibbs, Bruce M. Psaty, Kazima B. Bulayeva, Bryan J. Traynor, Vilmundur Gudnason, Jessika E. Sussmann, Alexander Teumer, Guillén Fernández, Katharina Wittfeld, Christophe Tzourio, Dennis van der Meer, Wolfgang Hoffmann, Sebastian Mohnke, David C. Liewald, Jordan W. Smoller, Theo G.M. van Erp, Marcel Van Der Brug, Dara M. Cannon, Lenore J. Launer, D. Ames, Juan C. Troncoso, Brenda W.J.H. Penninx, Dhananjay Vaidya, Thomas D. Dyer, Marie-José van Tol, Han G. Brunner, Andrew Singleton, Lavinia Athanasiu, Adam M. Brickman, Eric Westman, P. Mecocci, Sandra Barral, Dick J. Veltman, Catharina A. Hartman, Benedicto Crespo-Facorro, Alexa S. Beiser, Vincent Chouraki, Nhat Trung Doan, Marieke Klein, Jaap Oosterlaan, Natalie A. Royle, John B.J. Kwok, Saud Alhusaini, Ingrid Melle, Roberto Toro, Ravi Duggirala, Allissa Dillman, Reinhold Schmidt, Lisa R. Yanek, Anbupalam Thalamuthu, Helena Schmidt, Derrek P. Hibar, Albert V. Smith, Jean-Luc Martinot, Thomas H. Wassink, Jennifer S. Richards, Oliver Martinez, Joshua L. Roffman, Sylvane Desrivières, Hilkka Soininen, Rene L. Olvera, Ole A. Andreassen, Diana Tordesillas-Gutiérrez, Claudia L. Satizabal, Owen Carmichael, Lianne Schmaal, Bernd Kraemer, Martine Hoogman, Daniah Trabzuni, Oliver Grimm, Andrew M. McIntosh, René S. Kahn, Nazanin Karbalai, Margaret J. Wright, Harald H.H. Göring, Martina Papmeyer, Roberto Roiz-Santiañez, Luigi Ferrucci, David A. Bennett, Kwangsik Nho, Gianpiero L. Cavalleri, Andreas Meyer-Lindenberg, Masashi Ikeda, Avram J. Holmes, Greig I. de Zubicaray, Andreas Heinz, Tatjana Rundek, Maria del C. Valdés Hernández, Dalia Kasperaviciute, Dan L. Longo, Matthew J. Huentelman, Wiepke Cahn, Beverly G. Windham, Michael A. Nalls, Philipp G. Sämann, Stella Trompet, Vidar M. Steen, Marc M. Bohlken, Christopher D. Whelan, Hilleke E. Hulshoff Pol, Susanne Erk, Dorret I. Boomsma, Dirk J. Heslenfeld, Masaki Fukunaga, D. Hoehn, Stephen M. Lawrie, Mark E. Bastin, Marco P. Boks, M. Mallar Chakravarty, M. R. Cookson, C. McDonald, Magda Tsolaki, Badri N. Vardarajan, Jason L. Stein, Jan K. Buitelaar, Erik G. Jönsson, Oliver Gruber, Robert Johnson, Jingyun Yang, Joshua C. Bis, J. Wouter Jukema, Tulio Guadalupe, Nina Romanczuk-Seiferth, Kjetil Nordbø Jørgensen, Henry Brodaty, Diane M. Becker, Anouk den Braber, Allison C. Nugent, Thomas Wolfers, John Hardy, Joanna M. Wardlaw, Michelle Luciano, Christine Macare, Dena G. Hernandez, D. Morris, John Blangero, Andrew J. Schork, Daniel R. Weinberger, Johanna Hass, Andrew Simmons, Micael Andersson, Lucija Abramovic, David S. Knopman, Mark Jenkinson, Roel A. Ophoff, Sanjay M. Sisodiya, Boris A. Gutman, Asta Håberg, Stephanie Le Hellard, Stéphanie Debette, Nicola J. Armstrong, Sarah E. Medland, Hans J. Grabe, Henry Völzke, Thomas E. Nichols, Manuel Mattheisen, Sven Cichon, Venkata S. Mattay, Ingrid Agartz, Stefan Ropele, Lorna M. Lopez, Hans van Bokhoven, Philip L. De Jager, Miguel E. Rentería, Laura Almasy, Arthur W. Toga, Michael Czisch, Florian Holsboer, Ryota Kanai, Nic J.A. van der Wee, Peter Kochunov, Perminder S. Sachdev, Andre F. Marquand, Christian Enzinger, Anderson M. Winkler, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Metacohorts Consortium, Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, sans affiliation, QIMR Berghofer Medical Research Institute, University of Washington [Seattle], Department of Psychiatry, Donders Centre for Neuroscience, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University Medical Center [Utrecht], Department of Neurology and Neurosurgery [Montreal], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Sahlgrenska University Hospital [Gothenburg], Department of Biomedical Engineering, Illinois Institute of Technology (IIT), Rush University Medical Center [Chicago], University of Edinburgh, Lagos State University (LASU), Assistance Publique - Hôpitaux de Marseille (APHM), University of Oslo (UiO), Department of medical sciences, Uppsala University-Molecular Medicine-Science for Life Laboratory, John P. Hussman Institute for Human Genomics, University of Miami Leonard M. Miller School of Medicine (UMMSM), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), Douglas Mental Health University Institute, McGill University = Université McGill [Montréal, Canada], Université Lille Nord de France (COMUE), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe d'imagerie neurofonctionnelle (GIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Haukeland University Hospital, University of Bergen (UiB), Ames Laboratory [Ames, USA], Iowa State University (ISU)-U.S. Department of Energy [Washington] (DOE), Johns Hopkins University School of Medicine [Baltimore], Language and Genetics Department [Nijmegen], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, International Max Planck Research School for Language Sciences (IMPRS ), Laboratory of Neuro Imaging [Los Angeles] (LONI), Department of Mathematics [UCLA], Georgia Institute of Technology [Atlanta], Medizinische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Germany, Greifswald University Hospital, Beijing Normal University (BNU), Aalborg University [Denmark] (AAU), UCL Institute of Neurology and Epilepsy Society, Department of Medicine, Imperial College London, Service d'Endocrinologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Medstar Research Institute, Clinical And Experimental Epilepsy, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Genomics, Life and Brain Center, University of Bonn, Institute of Human Genetics, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], VU University Medical Center [Amsterdam], Indiana University School of Medicine, Indiana University System, Indiana Alzheimer Disease Center, Indiana University System-Indiana University System, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Department of Neurology, Statistical Genetics Group, Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], Department of Neurology [Austria], Medical University Graz, Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, INSERM, Neuroepidemiology U708, Bordeaux, France, Department of Neurosciences [San Diego], University of California [San Diego] (UC San Diego), Department of Cognitive Sciences [San Diego], Wuhan University [China], Plymouth University, Dpt of Psychiatry [New Haven], Yale University School of Medicine, Queensland Institute of Medical Research, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Department of Genetics, King Faisal Specialist Hospital and Research Centre, Depts of Radiology, Leiden University Medical Center (LUMC), University of Twente [Netherlands], Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), RCMG Ghent, Universiteit Gent = Ghent University [Belgium] (UGENT), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), National Institutes of Health [Bethesda] (NIH), Biospective [Montréal], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Université de Lille, Department of Clinical Genetics, Department of Experimental Physics, National University of Ireland Maynooth (Maynooth University), Texas Biomedical Research Institute [San Antonio, TX], The University of Texas Health Science Center at Houston (UTHealth), 849 Department of Human Genetics, Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Dementia Collaborative Research Centre, Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Department of Psychiatry [Boston], Massachusetts General Hospital [Boston], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], The Mind Research Network, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Division of Molecular and Cellular Therapeutics, Northwestern Polytechnical University [Xi'an] (NPU), Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Division of Medical Genetics, University of Basel (Unibas), Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Trinity College Dublin-St. James's Hospital, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], York Structural Biology Laboratory, Department of Chemistry, University of York [York, UK], Harvard Medical School [Boston] (HMS), Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], School of Psychology, University of Queensland, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratory of Neurogenetics, Department of Genomics, Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), École des hautes études en sciences sociales (EHESS), Department of Radiology, Mayo Clinic, Robertson Centre for Biostatistics, University of Glasgow, Human Genetics Center, Department of Medical and Molecular Genetics, Rensselaer Polytechnic Institute (RPI), Department of Physics, Okayama University, Okayama University, University of New Haven [Connecticut], Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Public Health Genomics Unit, Department of Mathematics, University of Colorado, University of Colorado [Boulder], Faculty of Medicine, University of Iceland [Reykjavik], Icelandic Heart Association, Kopavogur, Iceland., University of Science, VNU-HCM, University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Department of Medical Genetics, HMNC Brain Health, University of Oxford [Oxford], University of Florida [Gainesville] (UF), Göteborgs Universitet (GU), Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Brain Centre Rudolf Magnus [Utrecht], School of Psychology, University of Sussex, Brighton BN1 9QH, UK, University of Sussex, Institute of Cognitive Neuroscience, University College of London [London] (UCL), Medical University of Łódź (MUL), Mayo Clinic [Rochester], University of Maryland School of Medicine, University of Maryland System-University of Maryland System-University of Maryland [Baltimore County] (UMBC), University of Maryland System, School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Université de Cergy Pontoise (UCP), Université Paris-Seine, Lymphocyte Cell Biology Unit, Laboratory of Genetics, Psychiatry Institute, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Department of Health and Human Services, Department of Life Sciences, Mathematical Sciences Institute (MSI), Australian National University (ANU), Centre for Advanced Imaging, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia (UNIPG), Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Medical Faculty [Mannheim], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, University of Mississippi Medical Center (UMMC), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Institute of Clinical Chemistry and Laboratory Medicine, Department of Statistics [Coventry], University of Warwick [Coventry], Delft University of Technology (TU Delft), Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), Osaka University [Osaka], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Cedars-Sinai Medical Center, Politecnico di Milano [Milan] (POLIMI), University of Applied Sciences [Munich], Dpt of Pharmacology and Personalised Medicine [Maastricht], Maastricht University [Maastricht], Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, National Institute of Aging, 3rd Department of Neurology, Aristotle University of Thessaloniki-General Hospital of Thessaloniki George Papanikolaou, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Genentech, Inc. [San Francisco], Psychiatry and Leiden Institute for Brain and Cognition, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Community Medicine, Berlin School of Mind and Brain [Berlin], Humboldt-Universität zu Berlin, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Centre for Population Health Sciences, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet [Stockholm], University of Pretoria [South Africa], University of Missouri [Columbia] (Mizzou), University of Missouri System, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], University of Southern California (USC), University of California (UC)-University of California (UC), Sans affiliation, Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], University of Toronto, Radboud University [Nijmegen], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universität Bonn = University of Bonn, Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), Yale School of Medicine [New Haven, Connecticut] (YSM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), King Faisal Specialist Hospital and Research Centre (KFSH & RC), Universiteit Leiden-Universiteit Leiden, University of Twente, University of California [Irvine] (UC Irvine), Universiteit Gent = Ghent University (UGENT), Centre épigénétique et destin cellulaire (EDC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], University of Oxford, University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Università degli Studi di Perugia = University of Perugia (UNIPG), University Hospital Mannheim | Universitätsmedizin Mannheim, Universität Leipzig-Universität Leipzig, University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, University of Eastern Finland, Universiteit Leiden, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt University Of Berlin, Radboud University [Nijmegen]-Radboud University [Nijmegen], School of Medicine / Clinical Medicine, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Other departments, Adult Psychiatry, ARD - Amsterdam Reproduction and Development, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], McGill University-McGill University, Sahlgrenska University Hospital, McGill University, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), University of Bergen (UIB), Iowa State University (ISU)-U.S. Department of Energy (DOE), Beijing Normal University, Karakter Child and Adolescent Psychiatry University Center Nijmegen, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Gènes, Synapses et Cognition, Ghent University [Belgium] (UGENT), National University of Ireland Maynooth (NUIM), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Okayama University [Okayama], University of Florida [Gainesville], Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Aristotle University of Thessaloniki-G. Papanikolaou Hospital, Humboldt Universität zu Berlin, University of Missouri [Columbia], Epidemiology, Radiology & Nuclear Medicine, Medical Informatics, Internal Medicine, Neurology, Biological Psychology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, Cognitive Psychology, IBBA, APH - Personalized Medicine, Amsterdam Neuroscience - Brain Imaging, MUMC+: DA Klinische Genetica (5), Klinische Genetica, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Anatomy and neurosciences, APH - Digital Health, Hal, GIN, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Universidad de Cantabria, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
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Male ,Netherlands Twin Register (NTR) ,Genome-wide association study ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit ,Spatial memory ,0302 clinical medicine ,610 Medicine & health ,Child ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Episodic memory ,Aged, 80 and over ,Subiculum ,220 Statistical Imaging Neuroscience ,COMMON VARIANTS ,ALZHEIMERS-DISEASE ,ddc:500 ,Alzheimer's disease ,genetics [Methionine Sulfoxide Reductases] ,Science ,Locus (genetics) ,genetics [Protein-Serine-Threonine Kinases] ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Alzheimer Disease ,ASTN2 protein, human ,Humans ,GENOME-WIDE ASSOCIATION ,METAANALYSIS ,Aged ,Glycoproteins ,Dentate gyrus ,MEMORY ,medicine.disease ,R1 ,030104 developmental biology ,nervous system ,Genetic Loci ,MSRB3 protein, human ,030217 neurology & neurosurgery ,0301 basic medicine ,General Physics and Astronomy ,genetics [Alzheimer Disease] ,Hippocampal formation ,Hippocampus ,Genome-wide association studies ,Taugasjúkdómar ,Cohort Studies ,DPP4 protein, human ,TEMPORAL-LOBE EPILEPSY ,BRAIN-REGIONS ,genetics [Dipeptidyl Peptidase 4] ,genetics [Nerve Tissue Proteins] ,Genetics ,Multidisciplinary ,Neurodegenerative diseases ,BIPOLAR DISORDER ,Organ Size ,Middle Aged ,SUBFIELDS ,Protein-Serine-Threonine Kinases ,growth & development [Hippocampus] ,Female ,genetics [Glycoproteins] ,Microtubule-Associated Proteins ,Medical Genetics ,Neuroinformatics ,Adult ,genetics [Microtubule-Associated Proteins] ,Adolescent ,SUSCEPTIBILITY LOCI ,Dipeptidyl Peptidase 4 ,genetics [Protein Serine-Threonine Kinases] ,Nerve Tissue Proteins ,Bioinformatik och systembiologi ,Protein Serine-Threonine Kinases ,Biology ,physiopathology [Alzheimer Disease] ,150 000 MR Techniques in Brain Function ,Young Adult ,MAST4 protein, human ,medicine ,Journal Article ,Erfðafræði ,Genetic Predisposition to Disease ,ddc:610 ,Medicinsk genetik ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Bioinformatics and Systems Biology ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SCCO.NEUR] Cognitive science/Neuroscience ,Rannsóknir ,General Chemistry ,Methionine Sulfoxide Reductases ,150 Psychology ,Genome-Wide Association Study - Abstract
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness., published version, peerReviewed
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- 2017
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27. The genome sequence of African rice (Oryza glaberrima) and evidence for independent domestication
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Seunghee Lee, Wolfgang Golser, Woojin Kim, Manyuan Long, Paul J. Sanchez, Thomas Wicker, Marina Wissotski, Kristi de Baynast, Jetty S.S. Ammiraju, Muhua Wang, Carlos A. Machado, Marie-Noelle Ndjiondjop, Andrea Zuccolo, Dave Kudrna, Carlos Eduardo Maldonado, Steve Rounsley, Kayode Sanni, Jose Luis Goicoechea, Nick Sisneros, Judith Carney, Klaus F. X. Mayer, Rosa Maria Cossu, Mingsheng Chen, Pradeep Reddy Marri, Jinfeng Chen, Olivier Panaud, Georg Haberer, Xiang Song, Chuanzhu Fan, Rod A. Wing, Yeisoo Yu, University of Zurich, Wing, Rod A, Ecology and Evolutionary Biology [Tucson] (EEB), University of Arizona, Helmholtz-Zentrum München (HZM), Graduate School of Comprehensive Human Sciences, Université de Tsukuba = University of Tsukuba, Laboratoire Génome et développement des plantes (LGDP), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Institute of Plant Biology, Department of Biology, Institute of Bioinformatics and System Biology (IBIS), Broad Institute [Cambridge], and Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT)
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Crops, Agricultural ,DNA, Plant ,[SDV]Life Sciences [q-bio] ,Oryza barthii ,Population ,Molecular Sequence Data ,Plant genetics ,Crops ,Genomics ,580 Plants (Botany) ,Oryza glaberrima ,Medical and Health Sciences ,Genome ,Article ,Population genomics ,10126 Department of Plant and Microbial Biology ,1311 Genetics ,Genetics ,Amino Acid Sequence ,Domestication ,ComputingMilieux_MISCELLANEOUS ,2. Zero hunger ,Agricultural ,Oryza sativa ,Base Sequence ,biology ,Genetic Variation ,food and beverages ,Oryza ,DNA ,Plant ,Sequence Analysis, DNA ,Biological Sciences ,biology.organism_classification ,Genetics, Population ,Africa ,Plant sciences ,Sequence Analysis ,Genome, Plant ,Developmental Biology - Abstract
Mingsheng Chen, Klaus Mayer, Steve Rounsley, Rod Wing and colleagues report the genome sequence of African rice (Oryza glaberrima), a different species than Asian rice. The authors resequenced 20 O. glaberrima accessions and 94 Oryza barthii accessions (the putative progenitor species of O. glaberrima), and their analyses support the hypothesis that O. glaberrima was domesticated in a single region along the upper Niger river. Supplementary information The online version of this article (doi:10.1038/ng.3044) contains supplementary material, which is available to authorized users., The cultivation of rice in Africa dates back more than 3,000 years. Interestingly, African rice is not of the same origin as Asian rice (Oryza sativa L.) but rather is an entirely different species (i.e., Oryza glaberrima Steud.). Here we present a high-quality assembly and annotation of the O. glaberrima genome and detailed analyses of its evolutionary history of domestication and selection. Population genomics analyses of 20 O. glaberrima and 94 Oryza barthii accessions support the hypothesis that O. glaberrima was domesticated in a single region along the Niger river as opposed to noncentric domestication events across Africa. We detected evidence for artificial selection at a genome-wide scale, as well as with a set of O. glaberrima genes orthologous to O. sativa genes that are known to be associated with domestication, thus indicating convergent yet independent selection of a common set of genes during two geographically and culturally distinct domestication processes. Supplementary information The online version of this article (doi:10.1038/ng.3044) contains supplementary material, which is available to authorized users.
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- 2014
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28. Distinct lineages of Ebola virus in Guinea during the 2014 West African epidemic
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Laure Diancourt, Etienne Simon-Loriere, Edward C. Holmes, Jan P. Buchmann, Gamou Fall, Matthias Vandenbogaert, Christiane Bouchier, Valérie Caro, Christian B. Matranga, N’Faly Magassouba, Oumar Faye, Sakoba Keita, Ousmane Faye, Jean-Michel Thiberge, Lamine Koivogui, Pardis C. Sabeti, Amadou A. Sall, Jean-Claude Manuguerra, Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Arbovirus et Virus de Fièvres Hémorragiques [Dakar, Sénégal], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut National de Santé Publique [Conakry, Guinée] (INSP), Ministère de la Santé [Conakry, Guinea], Université Gamal Abdel Nasser de Conakry, Ministry of Health [Guinée], Cellule d'Intervention Biologique d'Urgence - Laboratory for Urgent Response to Biological Threats (CIBU), Institut Pasteur [Paris] (IP), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Génomique (Plate-Forme) - Genomics Platform, Génotypage des Pathogènes et Santé Publique (Plate-forme) (PF8), The University of Sydney, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Harvard University, This study was supported by the Pasteur Ebola Task Force (PETF) and has also received funding from the French government’s Investissement d’Avenir programme, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant number ANR-10-LABX-62-IBEID) and Institut Pasteur de Dakar. We are grateful to all members of the PETF for their support, and in particular F. Rey and K. Victoir. High-throughput sequencing was performed on the Genomics Platform of Institut Pasteur, member of ‘France Génomique’ consortium (ANR10-INBS-09-08)., We thank L. Ma for technical assistance and Institut Pasteur Clinical Research Department for their help with ethical approval procedures. E.C.H. is supported by an NHMRC Australia fellowship., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
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Glycosylation ,Lineage (genetic) ,[SDV]Life Sciences [q-bio] ,Molecular Sequence Data ,Genome, Viral ,Biology ,Mali ,medicine.disease_cause ,Virus ,Sierra Leone ,Sierra leone ,Evolution, Molecular ,Phylogenetics ,medicine ,Humans ,Phylogeny ,Glycoproteins ,Multidisciplinary ,Ebola virus ,Phylogenetic tree ,Transmission (medicine) ,Viral Core Proteins ,Mucins ,Genetic Variation ,Outbreak ,Hemorrhagic Fever, Ebola ,Nucleocapsid Proteins ,Ebolavirus ,RNA-Dependent RNA Polymerase ,Virology ,Protein Structure, Tertiary ,Nucleoproteins ,Mutation ,Guinea - Abstract
International audience; An epidemic of Ebola virus disease of unprecedented scale has been ongoing for more than a year in West Africa. As of 29 April 2015, there have been 26,277 reported total cases (of which 14,895 have been laboratory confirmed) resulting in 10,899 deaths. The source of the outbreak was traced to the prefecture of Guéckédou in the forested region of southeastern Guinea. The virus later spread to the capital, Conakry, and to the neighbouring countries of Sierra Leone, Liberia, Nigeria, Senegal and Mali. In March 2014, when the first cases were detected in Conakry, the Institut Pasteur of Dakar, Senegal, deployed a mobile laboratory in Donka hospital to provide diagnostic services to the greater Conakry urban area and other regions of Guinea. Through this process we sampled 85 Ebola viruses (EBOV) from patients infected from July to November 2014, and report their full genome sequences here. Phylogenetic analysis reveals the sustained transmission of three distinct viral lineages co-circulating in Guinea, including the urban setting of Conakry and its surroundings. One lineage is unique to Guinea and closely related to the earliest sampled viruses of the epidemic. A second lineage contains viruses probably reintroduced from neighbouring Sierra Leone on multiple occasions, while a third lineage later spread from Guinea to Mali. Each lineage is defined by multiple mutations, including non-synonymous changes in the virion protein 35 (VP35), glycoprotein (GP) and RNA-dependent RNA polymerase (L) proteins. The viral GP is characterized by a glycosylation site modification and mutations in the mucin-like domain that could modify the outer shape of the virion. These data illustrate the ongoing ability of EBOV to develop lineage-specific and potentially phenotypically important variation.
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- 2015
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29. SCRIB and PUF60 Are Primary Drivers of the Multisystemic Phenotypes of the 8q24.3 Copy-Number Variant
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Jacques S. Beckmann, Christelle Golzio, Nicholas Katsanis, Andrew Dauber, Małgorzata J.M. Nowaczyk, Susan Zeesman, Joel N. Hirschhorn, Francine M. Jodelka, Jill A. Rosenfeld, Danielle Martinet, Bruno Leheup, Cécile Guenot, Michelle L. Hastings, Susanne Kjaergaard, Sébastien Jacquemont, Janice Zunich, Maria Kibaek, UL, NGERE, Division of Endocrinology, Children's Hospital Boston, Harvard Medical School, Harvard Medical School [Boston] (HMS), Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Center for Human Disease Modeling, Duke University [Durham], Service de Génétique Médicale [CHUV Lausanne], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Service de Génétique Clinique [CHUV Lausanne], Department of Cell Biology and Anatomy [Chicago Medical School · Rosalind Franklin University], Chicago Medical School [Rosalind Franklin University], Rosalind Franklin University-Rosalind Franklin University, Department of Pediatrics [Odense University Hospital], Odense University Hospital, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Service de Génétique Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), McMaster University [Hamilton, Ontario], PerkinElmer, Inc., Indiana University School of Medicine, Indiana University System-Indiana University System, and Dept of Genetics, Harvard Medical School
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Male ,Microcephaly ,Developmental Disabilities ,[SDV]Life Sciences [q-bio] ,medicine.disease_cause ,0302 clinical medicine ,Genetics(clinical) ,Copy-number variation ,Child ,Zebrafish ,Genetics (clinical) ,Genetics ,0303 health sciences ,Mutation ,Chromosome Mapping ,RNA-Binding Proteins ,Phenotype ,[SDV] Life Sciences [q-bio] ,Child, Preschool ,Gene Knockdown Techniques ,RNA splicing ,Female ,RNA Splicing Factors ,Erratum ,Chromosomes, Human, Pair 8 ,SCRIB ,Adolescent ,DNA Copy Number Variations ,Biology ,Article ,03 medical and health sciences ,Intellectual Disability ,medicine ,Animals ,Humans ,Allele ,Alleles ,030304 developmental biology ,Tumor Suppressor Proteins ,Membrane Proteins ,medicine.disease ,Human genetics ,Genetic architecture ,Repressor Proteins ,Gene Deletion ,030217 neurology & neurosurgery ,HeLa Cells - Abstract
International audience; Copy-number variants (CNVs) represent a significant interpretative challenge, given that each CNV typically affects the dosage of multiple genes. Here we report on five individuals with coloboma, microcephaly, developmental delay, short stature, and craniofacial, cardiac, and renal defects who harbor overlapping microdeletions on 8q24.3. Fine mapping localized a commonly deleted 78 kb region that contains three genes: SCRIB, NRBP2, and PUF60. In vivo dissection of the CNV showed discrete contributions of the planar cell polarity effector SCRIB and the splicing factor PUF60 to the syndromic phenotype, and the combinatorial suppression of both genes exacerbated some, but not all, phenotypic components. Consistent with these findings, we identified an individual with microcephaly, short stature, intellectual disability, and heart defects with a de novo c.505C>T variant leading to a p.His169Tyr change in PUF60. Functional testing of this allele in vivo and in vitro showed that the mutation perturbs the relative dosage of two PUF60 isoforms and, subsequently, the splicing efficiency of downstream PUF60 targets. These data inform the functions of two genes not associated previously with human genetic disease and demonstrate how CNVs can exhibit complex genetic architecture, with the phenotype being the amalgam of both discrete dosage dysfunction of single transcripts and also of binary genetic interactions.
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- 2013
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30. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals
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Oliver J. Rando, Fengyun Sun, Emiliano P. Ricci, Clémence Belleannée, Lucas Fauquier, Manuel Garber, Ryan W. Serra, Ana Bošković, Xin Zhiguo Li, Xin Y. Bing, Benjamin R. Carone, Lina Song, Craig C. Mello, Melissa J. Moore, Alper Kucukural, Alan G. Derr, Jeremy M. Shea, Robert Sullivan, Colin C. Conine, Upasna Sharma, Conseil National de Recherches Canada (CNRC), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Faculté de Médecine, Centre Hospitalier de l'Université de Laval (CHUL), Istituto Nazionale di Fisica della Materia, Dipartimento di Scienza dei Materiali, Key Laboratory of Ocean Circulation and Waves, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China, Université Paris Diderot - Paris 7 (UPD7), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)
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0301 basic medicine ,Male ,Small RNA ,endocrine system ,Retroelements ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,Article ,03 medical and health sciences ,Mice ,Testis ,medicine ,Diet, Protein-Restricted ,Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Gene ,reproductive and urinary physiology ,Genetics ,Regulation of gene expression ,Epididymis ,Multidisciplinary ,urogenital system ,RNA ,Embryo ,RNA, Transfer, Gly ,Sperm ,Spermatozoa ,Cell biology ,Sperm Maturation ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Blastocyst ,Gene Expression Regulation ,Fertilization ,Transfer RNA - Abstract
Offspring affected by sperm small RNAs Paternal dietary conditions in mammals influence the metabolic phenotypes of offspring. Although prior work suggests the involvement of epigenetic pathways, the mechanisms remains unclear. Two studies now show that altered paternal diet affects the level of small RNAs in mouse sperm. Chen et al. injected sperm transfer RNA (tRNA) fragments from males that had been kept on a high-fat diet into normal oocytes. The progeny displayed metabolic disorders and concomitant alteration of genes in metabolic pathways. Sharma et al. observed the biogenesis and function of small tRNA-derived fragments during sperm maturation. Further understanding of the mechanisms by which progeny are affected by parental exposure may affect human diseases such as diet-induced metabolic disorders. Science , this issue p. 397 , p. 391
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- 2016
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31. Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition
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Massimo Iavarone, Ganesh Gunasekaran, Lan Wei, Takaaki Higashi, Hiroki Hoshida, Thomas F. Baumert, Augusto Villanueva, Rosa S. Kim, Anna P. Koh, Suguru Yamada, Scott L. Friedman, Xiaochen Sun, Bin Zhang, Milind Mahajan, Wan-Long Chuang, Angelo Sangiovanni, Yujin Hoshida, Derek J. Erstad, C Billie Bian, Myron E. Schwarz, Won-Min Song, Shigeki Nakagawa, Youngmin A. Lee, Gretchen Bain, Hideo Baba, Masahiro Kobayashi, Noor B. Ahmad, Bryan C. Fuchs, Gregory Y. Lauwers, Michael Lanuti, Kenneth K. Tanabe, Anu Venkatesh, Massimo Colombo, Mohamed El-Abtah, Sarani Ghoshal, Raymond T. Chung, Andrew M. Tager, Josep M. Llovet, Hiromitsu Kumada, Venugopalan D. Nair, Ming-Lung Yu, Chia-Yen Dai, Nicolas Goossens, Aravind Subramanian, Toru Beppu, Universitat de Barcelona, Department of Medicine [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Gastroenterological Surgery [Kumamoto, Japan], Kumamoto University-Graduate School of Medical Sciences [Kumamoto, Japan], Division of Surgical Oncology [Boston, MA, USA], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital Cancer Center [Boston, MA, USA], Department of Genetics and Genomic Sciences, Division of Gastroenterology and Hepatology [Geneva, Switzerland], Geneva University Hospital (HUG), PharmAkea Therapeutics [San Diego, CA, USA], Department of Pathology [Boston, MA, USA], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Recanati/Miller Transplantation Institute [New York, NY, USA], Department of Internal Medicine and Hepatitis Center [Kaohsiung, Taiwan] (Hepatobiliary Division), Kaohsiung Medical University Hospital [Taiwan], Center for Infectious Disease and Cancer Research [Kaohsiung, Taiwan], Kaohsiung Medical University [Kaohsiung, Taïwan] (KMU), Institute of Biomedical Sciences [Kaohsiung, Taiwan], National Sun Yat-Sen University (NSYSU), Department of Hepatology [Tokyo, Japan], Toranomon Hospital [Tokyo, Japan], Department of Neurology [New York, NY, USA], Division of Thoracic Surgery [Boston, MA, USA], M. & A. Migliavacca Center for Liver Disease [Milan, Italy] (1st Division of Gastroenterology), University of Milan-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Cancer Program [Cambridge, MA, USA], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT)-Broad Institute [Cambridge, MA, USA], Pulmonary and Critical Care Unit [Boston, MA, USA], Massachusetts General Hospital [Boston]-Center for Immunology and Inflammatory Diseases [Boston, MA, USA], Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle hépato-digestif [Strasbourg], Nouvel Hôpital Civil, Hospices Civils de Strasbourg-Institut Hospitalo-Universitaire de strasbourg, Gastrointestinal Division [Boston, MA, USA] (Liver Center - Department of Medicine), S.N. was supported by Uehara Memorial Foundation. N.G. was supported by FLAGS foundation, Nuovo-Soldati Cancer Research Foundation, and an advanced training grant from Geneva University Hospital. M.Y., W.-L.C., and C.-Y.D. were supported partially by Kaohsiung Medical University ‘‘Aim for the Top Universities Grant, grant No. KMU-TP103E06 & No. KMU-TP103E07 & No. KMUTP103E08,’’ and by a grant from Kaohsiung Medical University Hospital (KMUH102-2T01). T.F.B. was supported by ARC, Paris, Institut Hospitalo-Universitaire, Strasbourg (IHUARC IHU201301187), Laboratory of Excellence HEPSYS (ANR-10-LABX-0028), and European Union (ERC-2014-AdG-671231- HEPCIR). R.T.C. was supported by NIH/NIDDK (DK078772, DK098079). B.C.F. was supported by NIH/NCI (CA140861), NIH/NIDDK (DK104956), and grant from American Institute for Cancer Research. Y.H. was supported by NIH/NIDDK (DK099558), Irma T. Hirschl Trust, Dr. Harold and Golden Lamport Research Award, European Union (ERC-2014-AdG-671231-HEPCIR), and U.S. Department of Defense (W81XWH-16-1-0363)., Massachusetts General Hospital Cancer Center [Boston, MA, USA]-Harvard Medical School [Boston] (HMS), daulny, anne, and Università degli Studi di Milano = University of Milan (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
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Liver Cirrhosis ,0301 basic medicine ,Cancer Research ,Cirrhosis ,Bioinformatics ,gene signature ,Transcriptome ,chemistry.chemical_compound ,Risk Factors ,Lysophosphatidic acid ,Gene Regulatory Networks ,cancer chemoprevention ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Liver Neoplasms ,hepatocellular carcinoma ,Hepatitis B ,3. Good health ,Oncology ,Hepatic cirrhosis ,Hepatocellular carcinoma ,Liver cancer ,Signal Transduction ,Carcinoma, Hepatocellular ,Cirrosi hepàtica ,Antineoplastic Agents ,Biology ,Article ,prognostic prediction ,Càncer de fetge ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Gene Expression Profiling ,Cancer ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Gene signature ,medicine.disease ,Xenograft Model Antitumor Assays ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,digestive system diseases ,Rats ,030104 developmental biology ,chemistry ,Lysophospholipids ,Steatohepatitis ,transcriptome ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Shigeki Nakagawa, Lan Wei and Won MinSong are co-first author.; International audience; Cirrhosis is a milieu that develops hepatocellular carcinoma (HCC), the second most lethal cancer worldwide. HCC prediction and prevention in cirrhosis are key unmet medical needs. Here we have established an HCC risk gene signature applicable to all major HCC etiologies: hepatitis B/C, alcohol, and non-alcoholic steatohepatitis. A transcriptome meta-analysis of >500 human cirrhotics revealed global regulatory gene modules driving HCC risk and the lysophosphatidic acid pathway as a central chemoprevention target. Pharmacological inhibition of the pathway in vivo reduced tumors and reversed the gene signature, which was verified in organotypic ex vivo culture of patient-derived fibrotic liver tissues. These results demonstrate the utility of clinical organ transcriptome to enable a strategy, namely, reverse-engineering precision cancer prevention.
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- 2016
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32. Whole-genome resequencing reveals loci under selection during chicken domestication
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Ellen Sherwood, Finn Hallböök, Jonas Eriksson, Bertrand Bed'Hom, Matthew T. Webster, Örjan Carlborg, Francois Besnier, Carl-Johan Rubin, Per Jensen, Liang Jiang, Michael C. Zody, Michèle Tixier-Boichard, Jennifer R. S. Meadows, Leif Andersson, Kerstin Lindblad-Toh, Max Ingman, Sojeong Ka, Ted Sharpe, Paul B. Siegel, Department of Medical Biochemistry and Microbiology, Uppsala University, Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Department of Cell and Molecular Biology, Karolinska Institutet [Stockholm], Department of Genetics and Pathology, The Rudbeck Laboratory, Department of Neuroscience, Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences (SLU), Génétique Animale et Biologie Intégrative (GABI), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Department of Physics, Chemistry and Biology [Linköping] (IFM), Linköping University (LIU), Department of Animal and Poultry Sciences [Blacksburg] (APSC), Virginia Tech [Blacksburg], Andersson, Leif, Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], Department of Animal Bredding and Genetics, and Institut National de la Recherche Agronomique (INRA)-AgroParisTech
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Male ,organismal biology ,animal structures ,chicken ,[SDV]Life Sciences [q-bio] ,Molecular Sequence Data ,ved/biology.organism_classification_rank.species ,selection ,Genomics ,Locus (genetics) ,Biology ,Polymorphism, Single Nucleotide ,Genome ,genomic ,03 medical and health sciences ,genetic adaptation ,Naturvetenskap ,evolution ,Genetic variation ,Animals ,Amino Acid Sequence ,Selection, Genetic ,Allele ,Domestication ,Model organism ,Gene ,Sequence Deletion ,030304 developmental biology ,Genetics ,0303 health sciences ,Multidisciplinary ,ved/biology ,0402 animal and dairy science ,Sequence Analysis, DNA ,04 agricultural and veterinary sciences ,Biological Evolution ,040201 dairy & animal science ,domestic animal ,Genetic Loci ,Evolutionary biology ,genetic ,Female ,Natural Sciences ,Chickens ,Sequence Alignment ,Research Article - Abstract
Background Selective breeding for genetic improvement is expected to leave distinctive selection signatures within genomes. The identification of selection signatures can help to elucidate the mechanisms of selection and accelerate genetic improvement. Fighting chickens have undergone extensive artificial selection, resulting in modifications to their morphology, physiology and behavior compared to wild species. Comparing the genomes of fighting chickens and wild species offers a unique opportunity for identifying signatures of artificial selection. Results We identified selection signals in 100-kb windows sliding in 10-kb steps by using two approaches: the pooled heterozygosity \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$({\text{H}}_{\text{p}} )$$\end{document}(Hp) and the fixation index \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$(F_{\text{ST}} )$$\end{document}(FST) between Xishuangbanna fighting chicken (YNLC) and Red Jungle Fowl. A total of 413 candidate genes were found to be putatively under selection in YNLC. These genes were related to traits such as growth, disease resistance, aggressive behavior and energy metabolism, as well as the morphogenesis and homeostasis of many tissues and organs. Conclusions This study reveals mechanisms and targets of artificial selection, which will contribute to improve our knowledge about the evolution of fighting chickens and facilitate future quantitative trait loci mapping. Electronic supplementary material The online version of this article (doi:10.1186/s12711-016-0239-4) contains supplementary material, which is available to authorized users.
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- 2010
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33. White Matter Lesion Progression
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Hofer, Edith, Cavalieri, Margherita, Bis, Joshua C., DeCarli, Charles, Fornage, Myriam, Sigurdsson, Sigurdur, Srikanth, Velandai, Trompet, Stella, Verhaaren, Benjamin F.J., Wolf, Chris, Yang, Qiong, Adams, Hieab H.H., Amouyel, Philippe, Beiser, Alex, Buckley, Brendan M., Callisaya, Michele, Chauhan, Ganesh, De Craen, Anton J.M., Dufouil, Carole, Van Duijn, Cornelia M., Ford, Ian, Freudenberger, Paul, Gottesman, Rebecca F., Gudnason, Vilmundur, Heiss, Gerardo, Hofman, Albert, Lumley, Thomas, Martinez, Oliver, Mazoyer, Bernard, Moran, Chris, Niessen, Wiro J., Phan, Thanh, Psaty, Bruce M., Satizabal, Claudia L., Sattar, Naveed, Schilling, Sabrina, Shibata, Dean K., Slagboom, P. Eline, Smith, Albert, Stott, David J., Taylor, Kent D., Thomson, Russell, Töglhofer, Anna M., Tzourio, Christophe, van Buchem, Mark, Wang, Jing, Westendorp, Rudi G.J., Gwen Windham, B., Vernooij, Meike W., Zijdenbos, Alex, Beare, Richard, Debette, Stéphanie, Ikram, M. Arfan, Jukema, J. Wouter, Launer, Lenore J., Longstreth, W. T., Mosley, Thomas H., Seshadri, Sudha, Schmidt, Helena, Schmidt, Reinhold, Department of Neurology, Medical University Graz, Graz, Austri, University of Washington [Seattle], Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Human Genetics Center, The University of Texas Health Science Center at Houston (UTHealth), Department of Medical Biochemistry and Microbiology, Uppsala University, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Monash University [Melbourne], Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia, University of Tasmania [Hobart, Australia] (UTAS), Interuniversity Cardiology Institute Netherlands, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Anhui University [Hefei], Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Boston University [Boston] (BU), Boston University School of Medicine (BUSM), INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, Department of neurology, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Molecular Biology & Biochemistry, Johns Hopkins University School of Medicine [Baltimore], Icelandic Heart Association, Kopavogur, Iceland., Faculty of Medicine, University of Iceland [Reykjavik], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department of Biostatistics, University of Washington, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Wellcome Trust - MRC Cambridge, Delft University of Technology (TU Delft), Group Health Research Institute, Group Health Cooperative, INSERM, Neuroepidemiology U708, Bordeaux, France, Department of Pathological Biochemistry, Royal Infirmary, Department for Internal Medicine, Staedtische Kliniken Moenchengladbach, Department of Radiology, University of Washington, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands Consortium for Healthy Aging, Leiden University Medical Center, Leiden, the Netherlands, Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria, Department of Radiology [Leiden, The Netherlands], Leids Universitair Medisch Centrum [Leiden, The Netherlands], Laboratoire d'Etude des NanoStructures et Imagerie de Surface (LENSIS), Service de physique de l'état condensé (SPEC - UMR3680), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Department of Gerontology and Geriatrics, Netherlands Consortium for Healthy Ageing, Department of Neurology [Rotterdam], Departments of Radiology and of Epidemiology [Rotterdam], Biospective [Montréal], Murdoch Children's Research Institute (MCRI), Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, University of Mississippi Medical Center (UMMC), Department of Neurology [Boston, USA], Boston University [Boston] (BU)-Boston University [Boston] (BU), Dpt of Pharmacology and Personalised Medicine [Maastricht], Maastricht University [Maastricht], University of California-University of California, Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
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white matter lesions ,[SCCO.NEUR]Cognitive science/Neuroscience ,aging ,magnetic resonance imaging ,cerebral small vessel diseases ,biological factors - Abstract
International audience; Background and Purpose—White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.Methods—Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies.Results—A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (P
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- 2015
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34. The study to understand the genetics of the acute response to metformin and glipizide in humans (SUGAR-MGH): design of a pharmacogenetic resource for type 2 diabetes
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Jennifer N. Todd, Andrew W. Taylor, Geoffrey A. Walford, Maegan Harden, Deborah J. Wexler, Jaclyn Davis, Melissa K. Thomas, Janet Lo, Varinderpal Kaur, Jose C. Florez, Ling Chen, Katherine R. Littleton, Rachel J. Ackerman, Rebecca R. Fanelli, Bindu Chamarthi, Paul L. Huang, Corinne Barbato, Liana K. Billings, Allison B. Goldfine, A. Sofia Warner, Elliot S. Stolerman, Alisa K. Manning, Allan F. Moore, Sabina Q. Khan, Richard W. Grant, Rita M. McCarthy, Margo S. Hudson, Chunmei Huang, Marlene Fernandez, Alicia M. Hernandez, Rosa Bui, Laurel Garber, Amelia Lanier, Natalia Colomo, [Walford,GA, Colomo,N, Todd,JN, Billings,LK, Fernandez,M, Warner,AS, Davis,J, Littleton,KR, Hernandez,AM, Fanelli,RR, Lanier,A, Ackerman,RJ, Khan,SQ, Stolerman,ES, Moore,AF, Kaur,V, Taylor,A, Chen,L, Manning,AK, Florez,JC] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America. [Walford,GA, Wexler,D, Thomas,MK, Florez,JC] Diabetes Research Center, Diabetes Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America. [Walford,GA, Huang,C, Huang,P, Lo,J, Goldfine,A, Florez,JC] Harvard Medical School, Boston, Massachusetts, United States of America. [Colomo,N] Department of Endocrinology and Nutrition. Hospital Universitario Regional de Málaga. Instituto de Investigación Biomédica de Málaga (IBIMA). Málaga, Spain. [Todd,JN] Boston Children’s Hospital, Boston, Massachusetts, United States of America. [Billings,LK, ] Division of Endocrinology and Metabolism, NorthShore University Health System, Evanston, Illinois, United States of America. [Chamarthi,B] Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America. [Chamarthi,B, McCarthy,RM, Hudson,MS] Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America. [Barbato,C, Bui,R, Garber,L, Goldine,A] Joslin Diabetes Center, Boston, Massachusetts, United States of America. [Harden,M] Genomics Platform, Broad Institute, Cambridge, Massachusetts, United States of America. [Grant,RW] Division of Research, Kaiser Permanente Northern California, Oakland, California, United States of America., This work was conducted with support from National Institutes of Health/NIDDK awards R01 DK088214, R03 DK077675, and P30 DK036836, from the Joslin Clinical Research Center from its philanthropic donors, and and the Harvard Catalyst: The Harvard Clinical and translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Awards M01-RR-01066, 1 UL1 RR025758-04 and 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers).
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Blood Glucose ,Male ,Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings] ,medicine.medical_treatment ,lcsh:Medicine ,Type 2 diabetes ,Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,Hipoglicemiantes ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Insulina ,Insulin ,lcsh:Science ,Genetics ,Glucose tolerance test ,Prueba de tolerancia a la glucosa ,Multidisciplinary ,medicine.diagnostic_test ,Predisposición genética a la enfermedad ,Middle Aged ,Polimorfismo de nucleótido único ,Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings] ,Metformin ,3. Good health ,Phenotype ,Treatment Outcome ,Chemicals and Drugs::Organic Chemicals::Amidines::Guanidines::Biguanides::Metformin [Medical Subject Headings] ,Female ,Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Pharmacology::Pharmacogenetics [Medical Subject Headings] ,Alelos ,Fenotipo ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Clinical Chemistry Tests::Blood Chemical Analysis::Glucose Tolerance Test [Medical Subject Headings] ,Transcription Factor 7-Like 2 Protein ,medicine.drug ,Research Article ,Adult ,Blood sugar ,Check Tags::Male [Medical Subject Headings] ,Hypoglycemia ,Polymorphism, Single Nucleotide ,Diabetes mellitus ,medicine ,Chemicals and Drugs::Biological Factors::Biological Markers [Medical Subject Headings] ,Named Groups::Persons::Age Groups::Adult [Medical Subject Headings] ,Proteína 2 similar al factor de transcripción 7 ,Humans ,Hypoglycemic Agents ,Genetic Predisposition to Disease ,Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings] ,Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings] ,Alleles ,Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pancreatic Hormones::Insulins [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings] ,Aged ,Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings] ,business.industry ,lcsh:R ,Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 2 [Medical Subject Headings] ,glipicida ,Glucose Tolerance Test ,medicine.disease ,Biomarcadores ,Check Tags::Female [Medical Subject Headings] ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::TCF Transcription Factors::Transcription Factor 7-Like 2 Protein [Medical Subject Headings] ,Diabetes Mellitus, Type 2 ,Pharmacogenetics ,Diabetes Mellitus, Tipo II ,Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Sulfones::Sulfonylurea Compounds::Glipizide [Medical Subject Headings] ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hypoglycemic Agents [Medical Subject Headings] ,lcsh:Q ,Resultado del tratamiento ,business ,Biomarkers ,Glipizide ,Glucosa sanguínea ,Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose::Blood Glucose [Medical Subject Headings] - Abstract
ClinicalTrials.gov NCT01762046; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; OBJECTIVE Genome-wide association studies have uncovered a large number of genetic variants associated with type 2 diabetes or related phenotypes. In many cases the causal gene or polymorphism has not been identified, and its impact on response to anti-hyperglycemic medications is unknown. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH, NCT01762046) is a novel resource of genetic and biochemical data following glipizide and metformin administration. We describe recruitment, enrollment, and phenotyping procedures and preliminary results for the first 668 of our planned 1,000 participants enriched for individuals at risk of requiring anti-diabetic therapy in the future. METHODS All individuals are challenged with 5 mg glipizide × 1; twice daily 500 mg metformin × 2 days; and 75-g oral glucose tolerance test following metformin. Genetic variants associated with glycemic traits and blood glucose, insulin, and other hormones at baseline and following each intervention are measured. RESULTS Approximately 50% of the cohort is female and 30% belong to an ethnic minority group. Following glipizide administration, peak insulin occurred at 60 minutes and trough glucose at 120 minutes. Thirty percent of participants experienced non-severe symptomatic hypoglycemia and required rescue with oral glucose. Following metformin administration, fasting glucose and insulin were reduced. Common genetic variants were associated with fasting glucose levels. CONCLUSIONS SUGAR-MGH represents a viable pharmacogenetic resource which, when completed, will serve to characterize genetic influences on pharmacological perturbations, and help establish the functional relevance of newly discovered genetic loci to therapy of type 2 diabetes. TRIAL REGISTRATION ClinicalTrials.gov NCT01762046. Yes
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- 2015
35. New genetic loci link adipose and insulin biology to body fat distribution
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Shungin, Dmitry, Winkler, Thomas W, Workalemahu, Tsegaselassie, Hartman, Catharina A, Duncan, Emma L, Ntzani, Evangelia E, Oei, Ling, Albagha, Omar M E, Amin, Najaf, Kemp, John P, Koller, Daniel L, Li, Guo, Liu, Ching-Ti, Minster, Ryan L, Hassinen, Maija, Moayyeri, Alireza, Vandenput, Liesbeth, Willner, Dana, Xiao, Su-Mei, Yerges-Armstrong, Laura M, Zheng, Hou-Feng, Alonso, Nerea, Eriksson, Joel, Kammerer, Candace M, Kaptoge, Stephen K, Hayward, Caroline, Leo, Paul J, Thorleifsson, Gudmar, Wilson, Scott G, Wilson, James F, Aalto, Ville, Alen, Markku, Aragaki, Aaron K, Aspelund, Thor, Center, Jacqueline R, Dailiana, Zoe, Heikkilä, Kauko, Duggan, David J, Garcia, Melissa, Garcia-Giralt, Natàlia, Giroux, Sylvie, Hallmans, Göran, Hocking, Lynne J, Husted, Lise Bjerre, Jameson, Karen A, Khusainova, Rita, Kim, Ghi Su, Herzig, Karl-Heinz, Kooperberg, Charles, Koromila, Theodora, Kruk, Marcin, Laaksonen, Marika, Lacroix, Andrea Z, Lee, Seung Hun, Leung, Ping C, Lewis, Joshua R, Masi, Laura, Mencej-Bedrac, Simona, Helmer, Quinta, Nguyen, Tuan V, Nogues, Xavier, Patel, Millan S, Prezelj, Janez, Rose, Lynda M, Scollen, Serena, Siggeirsdottir, Kristin, Smith, Albert V, Svensson, Olle, Trompet, Stella, Hillege, Hans L, Trummer, Olivia, van Schoor, Natasja M, Woo, Jean, Zhu, Kun, Balcells, Susana, Brandi, Maria Luisa, Buckley, Brendan M, Cheng, Sulin, Christiansen, Claus, Cooper, Cyrus, Holmen, Oddgeir, Dedoussis, George, Ford, Ian, Frost, Morten, Goltzman, David, González-Macías, Jesús, Kähönen, Mika, Karlsson, Magnus, Khusnutdinova, Elza, Koh, Jung-Min, Kollia, Panagoula, Hunt, Steven C, Langdahl, Bente Lomholt, Leslie, William D, Lips, Paul, Ljunggren, Östen, Lorenc, Roman S, Marc, Janja, Mellström, Dan, Obermayer-Pietsch, Barbara, Olmos, José M, Pettersson-Kymmer, Ulrika, Isaacs, Aaron, Reid, David M, Riancho, José A, Ridker, Paul M, Rousseau, François, Slagboom, P Eline, Tang, Nelson L S, Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, María T, Wu, Joseph M W, Ittermann, Till, Aulchenko, Yurii S, Castano-Betancourt, Martha, Grundberg, Elin, Herrera, Lizbeth, Ingvarsson, Thorvaldur, Johannsdottir, Hrefna, Kwan, Tony, Li, Rui, Luben, Robert, Medina-Gómez, Carolina, James, Alan L, Palsson, Stefan Th, Reppe, Sjur, Rotter, Jerome I, Sigurdsson, Gunnar, van Meurs, Joyce B J, Verlaan, Dominique, Williams, Frances M K, Wood, Andrew R, Zhou, Yanhua, Gautvik, Kaare M, Johansson, Ingegerd, Pastinen, Tomi, Raychaudhuri, Soumya, Cauley, Jane A, Chasman, Daniel I, Clark, Graeme R, Cummings, Steven R, Danoy, Patrick, Dennison, Elaine M, Eastell, Richard, Eisman, John A, Juliusdottir, Thorhildur, Gudnason, Vilmundur, Hofman, Albert, Jackson, Rebecca D, Jones, Graeme, Jukema, J Wouter, Khaw, Kay-Tee, Lehtimäki, Terho, Liu, Yongmei, Lorentzon, Mattias, McCloskey, Eugene, Kalafati, Ioanna-Panagiota, Mitchell, Braxton D, Nandakumar, Kannabiran, Nicholson, Geoffrey C, Oostra, Ben A, Peacock, Munro, Pols, Huibert A P, Prince, Richard L, Raitakari, Olli, Reid, Ian R, Robbins, John, Kinnunen, Leena, Sambrook, Philip N, Sham, Pak Chung, Shuldiner, Alan R, Tylavsky, Frances A, van Duijn, Cornelia M, Wareham, Nick J, Cupples, L Adrienne, Econs, Michael J, Evans, David M, Harris, Tamara B, Koenig, Wolfgang, Kung, Annie Wai Chee, Psaty, Bruce M, Reeve, Jonathan, Spector, Timothy D, Streeten, Elizabeth A, Zillikens, M Carola, Thorsteinsdottir, Unnur, Ohlsson, Claes, Karasik, David, Richards, J Brent, Kooner, Ishminder K, Brown, Matthew A, Stefansson, Kari, Uitterlinden, André G, Ralston, Stuart H, Ioannidis, John P A, Kiel, Douglas P, Rivadeneira, Fernando, Sandholm, Niina, Salem, Rany M, McKnight, Amy Jayne, Kratzer, Wolfgang, Brennan, Eoin P, Forsblom, Carol, Isakova, Tamara, McKay, Gareth J, Williams, Winfred W, Sadlier, Denise M, Mäkinen, Ville-Petteri, Swan, Elizabeth J, Palmer, Cameron, Boright, Andrew P, Lamina, Claudia, Ahlqvist, Emma, Deshmukh, Harshal A, Keller, Benjamin J, Huang, Huateng, Ahola, Aila, Fagerholm, Emma, Gordin, Daniel, Harjutsalo, Valma, He, Bing, Heikkilä, Outi, Buchkovich, Martin L, Leander, Karin, Hietala, Kustaa, Kytö, Janne, Lahermo, Päivi, Lehto, Markku, Österholm, Anne-May, Parkkonen, Maija, Pitkäniemi, Janne, Rosengård-Bärlund, Milla, Saraheimo, Markku, Sarti, Cinzia, Lee, Nanette R, Söderlund, Jenny, Soro-Paavonen, Aino, Syreeni, Anna, Thorn, Lena M, Tikkanen, Heikki, Tolonen, Nina, Tryggvason, Karl, Tuomilehto, Jaakko, Wadén, Johan, Gill, Geoffrey V, Lichtner, Peter, Prior, Sarah, Guiducci, Candace, Mirel, Daniel B, Taylor, Andrew, Hosseini, Mohsen, Parving, Hans-Henrik, Rossing, Peter, Tarnow, Lise, Ladenvall, Claes, Alhenc-Gelas, François, Lind, Lars, Lefebvre, Pierre, Rigalleau, Vincent, Roussel, Ronan, Tregouet, David-Alexandre, Maestroni, Anna, Maestroni, Silvia, Falhammar, Henrik, Gu, Tianwei, Möllsten, Anna, Cimponeriu, Dan, Lindström, Jaana, Mihai, Ioana, Mota, Maria, Mota, Eugen, Serafinceanu, Cristian, Stavarachi, Monica, Hanson, Robert L, Nelson, Robert G, Kretzler, Matthias, Colhoun, Helen M, Panduru, Nicolae Mircea, Lobbens, Stéphane, Gu, Harvest F, Brismar, Kerstin, Zerbini, Gianpaolo, Hadjadj, Samy, Marre, Michel, Groop, Leif, Lajer, Maria, Bull, Shelley B, Waggott, Daryl, Paterson, Andrew D, Savage, David A, Bain, Stephen C, Martin, Finian, Hirschhorn, Joel N, Godson, Catherine, Florez, Jose C, Groop, Per-Henrik, Maxwell, Alexander P, Willer, Cristen J, Schmidt, Ellen M, Mach, François, Sengupta, Sebanti, Peloso, Gina M, Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Mora, Samia, Beckmann, Jacques S, Bragg-Gresham, Jennifer L, Magnusson, Patrik Ke, Chang, Hsing-Yi, Demirkan, Ayşe, Den Hertog, Heleen M, Do, Ron, Donnelly, Louise A, Ehret, Georg B, Esko, Tõnu, Feitosa, Mary F, Ferreira, Teresa, Fischer, Krista, Mahajan, Anubha, Fontanillas, Pierre, Fraser, Ross M, Freitag, Daniel F, Gurdasani, Deepti, Hyppönen, Elina, Jackson, Anne U, Johansson, Åsa, Johnson, Toby, Heard-Costa, Nancy L, McArdle, Wendy L, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E, Li, Xiaohui, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K E, Mangino, Massimo, Mihailov, Evelin, Montasser, May E, Menni, Cristina, Müller-Nurasyid, Martina, Nolte, Ilja M, O'Connell, Jeffrey R, Palmer, Cameron D, Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Service, Susan K, Shah, Sonia, Merger, Sigrun, Sidore, Carlo, Song, Ci, Strawbridge, Rona J, Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M, Van den Herik, Evita G, Voight, Benjamin F, Volcik, Kelly A, Waite, Lindsay L, Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Inês, Been, Latonya F, Bolton, Jennifer L, Milani, Lili, Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S, Cesana, Giancarlo, Dimitriou, Maria, Doney, Alex S F, Döring, Angela, Elliott, Paul, Epstein, Stephen E, Eyjolfsson, Gudmundur Ingi, Mills, Rebecca, Gigante, Bruna, Goodarzi, Mark O, Grallert, Harald, Gravito, Martha L, Groves, Christopher J, Hartikainen, Anna-Liisa, Hernandez, Dena, Hicks, Andrew A, Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R, Kaleebu, Pontiano, Kastelein, John J P, Kim, Eric, Klopp, Norman, Komulainen, Pirjo, Monda, Keri L, Kumari, Meena, Langenberg, Claudia, Lin, Shih-Yi, Loos, Ruth J F, Meisinger, Christa, Mooijaart, Simon P, Müller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V M, Nsubuga, Rebecca N, Olafsson, Isleifur, Ong, Ken K, Palotie, Aarno, Papamarkou, Theodore, Pomilla, Cristina, Mühleisen, Thomas W, Pouta, Anneli, Rader, Daniel J, Reilly, Muredach P, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Scharnagl, Hubert, Seeley, Janet, Roman, Tamara S, Mulas, Antonella, Silander, Kaisa, Stančáková, Alena, Stirrups, Kathleen, Swift, Amy J, Tiret, Laurence, Uitterlinden, Andre G, van Pelt, L Joost, Vedantam, Sailaja, Wainwright, Nicholas, Wijmenga, Cisca, Müller, Gabriele, Wild, Sarah H, Willemsen, Gonneke, Wilsgaard, Tom, Young, Elizabeth H, Zhao, Jing Hua, Adair, Linda S, Arveiler, Dominique, Assimes, Themistocles L, Bandinelli, Stefania, Bennett, Franklyn, Bochud, Murielle, Boehm, Bernhard O, Boomsma, Dorret I, Borecki, Ingrid B, Bornstein, Stefan R, Bovet, Pascal, Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chen, Yii-Der Ida, Collins, Francis S, Cooper, Richard S, Danesh, John, de Faire, Ulf, Feranil, Alan B, Ferrières, Jean, Ferrucci, Luigi, Nalls, Michael A, Freimer, Nelson B, Gieger, Christian, Groop, Leif C, Gyllensten, Ulf, Hamsten, Anders, Hingorani, Aroon, Hovingh, G Kees, Hsiung, Chao Agnes, Humphries, Steve E, Hveem, Kristian, Iribarren, Carlos, Järvelin, Marjo-Riitta, Jula, Antti, Kaprio, Jaakko, Glorioso, Nicola, Kesäniemi, Antero, Kivimaki, Mika, Kooner, Jaspal S, Koudstaal, Peter J, Krauss, Ronald M, Kuh, Diana, Kuusisto, Johanna, Kyvik, Kirsten O, Laakso, Markku, Lakka, Timo A, Lindgren, Cecilia M, Martin, Nicholas G, März, Winfried, McCarthy, Mark I, McKenzie, Colin A, Meneton, Pierre, Metspalu, Andres, Moilanen, Leena, Morris, Andrew D, Olden, Matthias, Munroe, Patricia B, Njølstad, Inger, Pedersen, Nancy L, Power, Chris, Pramstaller, Peter P, Price, Jackie F, Quertermous, Thomas, Rauramaa, Rainer, Saleheen, Danish, Rayner, Nigel W, Salomaa, Veikko, Sanghera, Dharambir K, Saramies, Jouko, Schwarz, Peter E H, Sheu, Wayne H-H, Siegbahn, Agneta, Spector, Tim D, Strachan, David P, Drong, Alexander W, Renstrom, Frida, Tayo, Bamidele O, Tremoli, Elena, Uusitupa, Matti, Vollenweider, Peter, Wallentin, Lars, Wareham, Nicholas J, Whitfield, John B, Wolffenbuttel, Bruce H R, Ried, Janina S, Ordovas, Jose M, Boerwinkle, Eric, Palmer, Colin N A, Franks, Paul W, Ripatti, Samuli, Sandhu, Manjinder S, Robertson, Neil R, Rich, Stephen S, Boehnke, Michael, Deloukas, Panos, Kathiresan, Sekar, Mohlke, Karen L, Ingelsson, Erik, Abecasis, Gonçalo R, Abecasis, Gonçalo, Caulfield, Mark, Chasman, Dan, Ehret, Georg, Johnson, Andrew, Johnson, Louise, Larson, Martin, Levy, Daniel, Munroe, Patricia, Newton-Cheh, Christopher, O'Reilly, Paul, Palmas, Walter, Psaty, Bruce, Rice, Kenneth, Smith, Albert, Snider, Harold, Tobin, Martin, Van Duijn, Cornelia, Verwoert, Germaine, Rice, Kenneth M, Johnson, Andrew D, Tobin, Martin D, Verwoert, Germaine C, Hwang, Shih-Jen, Pihur, Vasyl, Scholtens, Salome, O'Reilly, Paul F, Teumer, Alexander, Glazer, Nicole L, Launer, Lenore, Aulchenko, Yurii, Heath, Simon, Sennblad, Bengt, Sõber, Siim, Parsa, Afshin, Arora, Pankaj, Dehghan, Abbas, Zhang, Feng, Lucas, Gavin, Peden, John F, Seufferlein, Thomas, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N, Fava, Cristiano, Fox, Ervin R, Sitlani, Colleen M, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H, Smith, Albert Vernon, Shi, Gang, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Nguyen, Khanh-Dung Hoang, Matullo, Giuseppe, Gaunt, Tom R, Onland-Moret, N Charlotte, Cooper, Matthew N, Platou, Carl G P, Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S, Kuznetsova, Tatiana, Stringham, Heather M, Uiterwaal, Cuno S P M, Adeyemo, Adebowale, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D, Sundström, Johan, Chang, Yen-Pei C, Steinle, Nanette I, Grobbee, Diederick E, Arking, Dan E, Kardia, Sharon L, Morrison, Alanna C, Najjar, Samer, Swertz, Morris A, Hadley, David, Brown, Morris J, Connell, John M, Hingorani, Aroon D, Day, Ian N M, Lawlor, Debbie A, Beilby, John P, Lawrence, Robert W, Clarke, Robert, Collins, Rory, Hopewell, Jemma C, Ongen, Halit, Dreisbach, Albert W, Li, Yali, Young, J. H., Bis, Joshua C, Syvänen, Ann-Christine, Chen, Ming-Huei, Pattaro, Cristian, Bolton, Judith A Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Frayling, Timothy M, Islam, Muhammad, Jafar, Tazeen H, Erdmann, Jeanette, Kulkarni, Smita R, Grässler, Jürgen, Howard, Philip, Thorand, Barbara, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Weder, Alan B, Sun, Yan V, Bergman, Richard N, Scott, Laura J, Peltonen, Leena, Vartiainen, Erkki, Brand, Stefan-Martin, Staessen, Jan A, Wang, Thomas J, Tomaschitz, Andreas, Burton, Paul R, Artigas, Maria Soler, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K, Rudock, Megan E, Heckbert, Susan R, Smith, Nicholas L, Troffa, Chiara, Wiggins, Kerri L, Doumatey, Ayo, Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margus, Kinra, Sanjay, Prabhakaran, Dorairajan, Tripathy, Vikal, Langefeld, Carl D, Rosengren, Annika, van Oort, Floor Va, Thelle, Dag S, Corsi, Anna Maria, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, Salako, Tunde, Iwai, Naoharu, Kita, Yoshikuni, Ogihara, Toshio, Verweij, Niek, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thomas, Wichmann, H-Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Vonk, Judith M, Scott, James, Sehmi, Joban S, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Stanèáková, Alena, Raffel, Leslie J, Yao, Jie, O'Donnell, Chris, Schwartz, Stephen M, Ikram, M Arfan, Longstreth, W. T., Mosley, Thomas H, Seshadri, Sudha, Shrine, Nick R G, Wain, Louise V, Wennauer, Roman, Morken, Mario A, Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A, Rasheed, Asif, Goel, Anuj, Watkins, Hugh, Bakker, Stephan J L, van Gilst, Wiek H, Janipalli, Charles S, Mani, K Radha, Yajnik, Chittaranjan S, Mattace-Raso, Francesco U S, Wojczynski, Mary K, Demirkan, Ayse, Lakatta, Edward G, Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Ong, Rick Twee-Hee, Dörr, Marcus, Kroemer, Heyo K, Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Day, Felix R, Zhang, Qunyuan, Zelenika, Diana, Zhai, Guangju, Meschia, James F, Sharma, Pankaj, Terzic, Janos, Kumar, M J Kranthi, Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E, Fowkes, F Gerald R, Charchar, Fadi J, Guo, Xiuqing, Rotimi, Charles, Bots, Michiel L, Brand, Eva, Samani, Nilesh J, Polasek, Ozren, Talmud, Philippa J, Nyberg, Fredrik, Laan, Maris, Palmer, Lyle J, van der Schouw, Yvonne T, Choi, Murim, Casas, Juan P, Vineis, Paolo, Ganesh, Santhi K, Wong, Tien Y, Tai, E Shyong, Rao, Dabeeru C, Eriksson, Per, Morris, Richard W, Dominiczak, Anna F, Marmot, Michael G, Miki, Tetsuro, Chandak, Giriraj R, Coresh, Josef, Navis, Gerjan, Folkersen, Lasse, Han, Bok-Ghee, Zhu, Xiaofeng, Melander, Olle, Gyllensten, Ulf B, Wright, Alan F, Franco-Cereceda, Anders, Farrall, Martin, Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J G, Altshuler, David, Gharavi, Ali G, Rettig, Rainer, Uda, Manuela, Witteman, Jacqueline C M, Hedman, Åsa K, Vasan, Ramachandran S, Larson, Martin G, Hivert, Marie-France, Caulfield, Mark J, Anderson, Carl A, Gordon, Scott D, Guo, Qun, Henders, Anjali K, Esko, Tonu, Huang, Jinyan, Lambert, Ann, Lee, Sang Hong, Kraft, Peter, Kennedy, Stephen H, Macgregor, Stuart, Missmer, Stacey A, Montgomery, Grant W, Morris, Andrew P, Nyholt, Dale R, Painter, Jodie N, Roseman, Fenella, Treloar, Susan A, Visscher, Peter M, Wallace, Leanne, Zondervan, Krina T, Alizadeh, Behrooz Z, de Boer, Rudolf A, Boezen, H Marike, Bruinenberg, Marcel, Karpe, Fredrik, Franke, Lude, van der Klauw, Melanie M, Ormel, Johan, Postma, Dirkje S, Rosmalen, Judith G M, Slaets, Joris P, Keildson, Sarah, Stolk, Ronald P, Scott, Robert A, Lagou, Vasiliki, Welch, Ryan P, Wheeler, Eleanor, Mägi, Reedik, Kiryluk, Krzysztof, Rehnberg, Emil, Rasmussen-Torvik, Laura J, Yengo, Loïc, Lecoeur, Cecile, Liang, Liming, Johnson, Paul C D, Hottenga, Jouke-Jan, Lifton, Richard P, Salo, Perttu, Timpson, Nicholas J, St Pourcain, Beate, Andrews, Jeanette S, Hui, Jennie, Bielak, Lawrence F, Ma, Baoshan, Zhao, Wei, Horikoshi, Momoko, Navarro, Pau, Esko, Tönu, McKnight, Amy J, Fall, Tove, Chen, Han, Robertson, Neil, Rybin, Denis, McPherson, Ruth, Willems, Sara M, Chines, Peter S, Kang, Hyun Min, Song, Kijoung, Croteau-Chonka, Damien C, An, Ping, Marullo, Letizia, Jansen, Hanneke, Oldehinkel, Albertine J, Min, Josine L, Pankow, James S, North, Kari E, Forouhi, Nita G, Edkins, Sarah, Varga, Tibor V, Oksa, Heikki, Antonella, Mulas, Moffatt, Miriam F, Kong, Augustine, Herder, Christian, Antti, Jula, Small, Kerrin, Miljkovic, Iva, Atalay, Mustafa, Kiess, Wieland, Murabito, Joanne M, Smit, Johannes H, Campbell, Susan, Fowkes, Gerard R, Nicholson, George, Kovacs, Peter, Zemunik, Tatijana, Basart, Hanneke V, Rathmann, Wolfgang, Maerz, Winfried, Peters, Annette, Province, Michael A, Hastie, Nicholas D, Olsson, Christian, Stumvoll, Michael, Waterworth, Dawn M, Watanabe, Richard M, de Geus, Eco J C, Penninx, Brenda W, Perry, John Rb, Reinmaa, Eva, Dedoussis, George V, Kutalik, Zoltán, Toenjes, Anke, Peyser, Patricia A, Körner, Antje, Keinanen-Kiukaanniemi, Sirkka M, Schadt, Eric E, Saaristo, Timo E, Dupuis, Josée, Sattar, Naveed, Cucca, Francesco, Balkau, Beverley, Froguel, Philippe, Jarvelin, Marjo-Riitta, Bouatia-Naji, Nabila, Stolk, Lisette, Meigs, James B, Ahmadi, Kourosh R, Ainali, Chrysanthi, Barrett, Amy, Vallejo, Edgar E, Bataille, Veronique, Bell, Jordana T, Buil, Alfonso, Dermitzakis, Emmanouil T, Dimas, Antigone S, Durbin, Richard, Glass, Daniel, Hassanali, Neelam, Westra, Harm-Jan, Ingle, Catherine, Knowles, David, Krestyaninova, Maria, Lowe, Christopher E, Meduri, Eshwar, di Meglio, Paola, Montgomery, Stephen B, Nestle, Frank O, Nica, Alexandra C, Nisbet, James, O'Rahilly, Stephen, Parts, Leopold, Potter, Simon, Sekowska, Magdalena, Shin, So-Youn, Consortium, ADIPOGen, Small, Kerrin S, Surdulescu, Gabriela, Travers, Mary E, Tsaprouni, Loukia, Tsoka, Sophia, Wilk, Alicja, Yang, Tsun-Po, Consortium, CARDIOGRAMplusC4D, Matise, Tara, Buyske, Steve, Higashio, Julia, Williams, Rasheeda, Nato, Andrew, Ambite, Jose Luis, Deelman, Ewa, Manolio, Teri, Hindorff, Lucia, Consortium, CKDGen, Heiss, Gerardo, Taylor, Kira, Franceschini, Nora, Avery, Christy, Graff, Misa, Lin, Danyu, Quibrera, Miguel, Cochran, Barbara, Kao, Linda, Umans, Jason, Consortium, GEFOS, Cole, Shelley, MacCluer, Jean, Person, Sharina, Pankow, James, Gross, Myron, Fornage, Myriam, Durda, Peter, Jenny, Nancy, Patsy, Bruce, Consortium, GENIE, Arnold, Alice, Buzkova, Petra, Crawford, Dana, Haines, Jonathan, Murdock, Deborah, Glenn, Kim, Brown-Gentry, Kristin, Thornton-Wells, Tricia, Dumitrescu, Logan, Jeff, Janina, GLGC, Bush, William S, Mitchell, Sabrina L, Goodloe, Robert, Wilson, Sarah, Boston, Jonathan, Malinowski, Jennifer, Restrepo, Nicole, Oetjens, Matthew, Fowke, Jay, Zheng, Wei, ICBP, Spencer, Kylee, Ritchie, Marylyn, Pendergrass, Sarah, Le Marchand, Loïc, Wilkens, Lynne, Park, Lani, Tiirikainen, Maarit, Kolonel, Laurence, Lim, Unhee, Cheng, Iona, Consortium, International Endogene, Wang, Hansong, Shohet, Ralph, Haiman, Christopher, Stram, Daniel, Henderson, Brian, Monroe, Kristine, Schumacher, Fredrick, Peters, Ulrike, Anderson, Garnet, Study, LifeLines Cohort, Carlson, Chris, Prentice, Ross, LaCroix, Andrea, Wu, Chunyuan, Carty, Cara, Gong, Jian, Rosse, Stephanie, Young, Alicia, Haessler, Jeff, Kocarnik, Jonathan, Investigators, MAGIC, Lin, Yi, Jackson, Rebecca, Duggan, David, Kuller, Lew, Perry, John R B, He, Chunyan, Sulem, Patrick, Consortium, MuTHER, Barbalic, Maja, Broer, Linda, Byrne, Enda M, Ernst, Florian, Gudbjartsson, Daniel F, McArdle, Patick F, Consortium, PAGE, Porcu, Eleonora, van Wingerden, Sophie, Zhuang, Wei V, Albrecht, Eva, Randall, Joshua C, Consortium, ReproGen, Lauc, Lovorka Barac, Boban, Mladen, Broekmans, Frank J, Burri, Andrea, Chanock, Stephen J, Chen, Constance, Cornelis, Marilyn C, Amouyel, Philippe, Corre, Tanguy, Coviello, Andrea D, d'Adamo, Pio, Davies, Gail, Deary, Ian J, Dedoussis, George V Z, Deloukas, Panagiotis, Ebrahim, Shah, Eiriksdottir, Gudny, Eriksson, Johan G, Fauser, Bart C J M, Ferreli, Liana, Folsom, Aaron R, Garcia, Melissa E, Gasparini, Paolo, Bakker, Stephan Jl, Glazer, Nicole, Hall, Per, Haller, Toomas, Hankinson, Susan E, Hass, Merli, Heath, Andrew C, Beilby, John, Janssens, A Cecile J W, Kardia, Sharon L R, Keyzer, Jules, Kolcic, Ivana, Lahti, Jari, Lai, Sandra, Laisk, Triin, Laven, Joop S E, Liu, Jianjun, Lopez, Lorna M, Louwers, Yvonne V, Marongiu, Mara, Blangero, John, Klaric, Irena Martinovic, Masciullo, Corrado, McKnight, Barbara, Medland, Sarah E, Melzer, David, Newman, Anne B, Paré, Guillaume, Peeters, Petra H M, Pistis, Giorgio, Plump, Andrew S, Pop, Victor J M, Räikkönen, Katri, Sala, Cinzia, Salumets, Andres, Smith, Jennifer A, Stacey, Simon N, Starr, John M, Stathopoulou, Maria G, Styrkarsdottir, Unnur, Tenesa, Albert, Scherag, André, Toniolo, Daniela, Tryggvadottir, Laufey, Tsui, Kim, Ulivi, Sheila, van Dam, Rob M, van Gils, Carla H, van Nierop, Peter, Vink, Jacqueline M, Voorhuis, Marlies, Waeber, Gérard, Wallaschofski, Henri, Wichmann, H Erich, Widen, Elisabeth, Wijnands-van Gent, Colette J M, Claudi-Boehm, Simone, Zgaga, Lina, Zygmunt, Marek, Arnold, Alice M, Buring, Julie E, Crisponi, Laura, Demerath, Ellen W, Hu, Frank B, Hunter, David J, Launer, Lenore J, Crawford, Dana C, 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Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Stolk, L., He, C., Sulem, P., Barbalic, M., Broer, L., Byrne, EM., Gudbjartsson, DF., McArdle, PF., Porcu, E., van Wingerden, S., Zhuang, W., Albrecht, E., Alizadeh, BZ., Lauc, LB., Broekmans, FJ., Burri, A., Chanock, SJ., Chen, C., Corre, T., Coviello, AD., d'Adamo, P., Davies, G., Deary, IJ., Ebrahim, S., Fauser, BC., Ferreli, L., Folsom, AR., Garcia, ME., Hall, P., Haller, T., Hankinson, SE., Hass, M., Heath, AC., Janssens, AC., Keyzer, J., Lahti, J., Lai, S., Laisk, T., Laven, JS., Liu, J., Lopez, LM., Louwers, YV., Marongiu, M., Klaric, IM., Masciullo, C., McKnight, B., Medland, SE., Melzer, D., Newman, AB., Paré, G., Peeters, PH., Plump, AS., Pop, VJ., Räikkönen, K., Salumets, A., Smith, JA., Stacey, SN., Starr, JM., Stathopoulou, MG., Tenesa, A., Thorand, B., Tryggvadottir, L., Tsui, K., van Dam RM., van Gils CH., van Nierop, P., Vink, JM., Voorhuis, M., Wallaschofski, H., Widen, E., Wijnands-van Gent CJ., Zgaga, L., Zygmunt, M., Arnold, AM., Buring, JE., Crisponi, L., Demerath, EW., Hunter, DJ., Schlessinger, D., Murray, A., Murabito, JM., Visser, JA., Lunetta, KL., Elks, CE., Cousminer, DL., Feenstra, B., Lin, P., van Wingerden SW., Smith, EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., Weedon, MN., Wichmann, H., Young, L., Zhuang, WV., Bierut, LJ., Boyd, HA., Department of Clinical Sciences, Lund University [Lund], Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Odontology, Umeå University, Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Sciences, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Laboratory of Image Science and Technology [Nanjing] (LIST), Southeast University [Jiangsu]-School of Computer Science and Engineering, Limnology, Ecology, Estonian Genome and Medicine, University of Tartu, Institute of Molecular and Cell Biology, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Institute of Medical Informatics, Biometry and Epidemiology, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Space Sciences Laboratory [Berkeley] (SSL), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, King‘s College London, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Molecular Genetics Section, University of Groningen [Groningen]-University Medical Centre Groningen, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Department of Pharmacy Sciences, Creighton University Medical Center, Medical Department III, Universität Leipzig, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Epidemiology, Erasmus Medical Centre, Netherlands Genomics Initiative (NGI), Netherlands Genomics Initiative, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Public Health and Clinical Medicine, Medstar Research Institute, Genetics and Pathology, Finnish Institute of Occupational Health, Epidemiology, University Medical Centre Groningen, Departments of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, University of California [Irvine] (UC Irvine), Department of Odontology, Cariology, Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Division of Cardiology, Geneva University Hospital (HUG), Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Anaesthesia and Intensive care, Royal Aberdeen Childrens Hospital, UCL Institute of neurology, UCL Institute of Neurology, Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], 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= University of Helsinki, Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Department of Pediatrics, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, MRC epidemiology Unit, Institute of Epidemiology, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Oncology, Queensland Brain Institute, University of Queensland [Brisbane], Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, 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(BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Endocrinology and Metabolism, The Churchill Hospital-Oxford Centre for Diabetes, Landsteiner Laboratory, Clinical Haematology, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Lund University Diabetes Centre-Lund University [Lund], Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Technical University of Denmark [Lyngby] (DTU), Université de Lausanne (UNIL), Universität Duisburg-Essen [Essen], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of California [Berkeley], University of California-University of California, Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig [Leipzig], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of California [Irvine] (UCI), German Research Center for Environmental Health, University of Bonn, Czech Academy of Sciences [Prague] (ASCR), Yale University School of Medicine, University of Oxford [Oxford], German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Laval University, Laval University [Québec], Turku University Hospital, Lausanne university hospital, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Helmholtz-Zentrum München (HZM), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Internal Medicine, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Medical Informatics, Obstetrics & Gynecology, Lund University [Lund]-Lund University Diabetes Centre, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institute of Medicine-University of Gothenburg (GU), Signalisation et Transports Ioniques Membranaires ( STIM ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Technical University of Denmark [Lyngby] ( DTU ), Laboratory of Image Science and Technology [Nanjing] ( LIST ), Department of Medical Epidemiology and Biostatistics ( MEB ), University of Lausanne, Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Erasmus MC, Space Sciences Laboratory [Berkeley] ( SSL ), Génomique Intégrative et Modélisation des Maladies Métaboliques ( EGID ), Université de Lille-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), University of Leipzig, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institute of Epidemiology [Neuherberg] ( EPI ), University of California [Irvine] ( UCI ), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Geneva University Hospital ( HUG ), Bonn Universität [Bonn], Indian Institute of Technology Kanpur ( IIT Kanpur ), The University of North Carolina at Chapel Hill, Université de Bonn, Wellcome Trust Sanger Institute, Harvard University School of Public Health, Czech Academy of Sciences [Prague] ( ASCR ), deCODE genetics, University of Groningen [Groningen]-University Medical Center Groningen-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Yale School of Medicine, National Heart and Lung Institute ( NHLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, University Medical Center Groningen, University of Cambridge [UK] ( CAM ), Wellcome Trust Centre for Human Genetics, University of Pisa [Pisa], University of Cambridge [UK] ( CAM ) -Institute of Metabolic Science, German Research Center for Environmental Health-Helmholtz-Zentrum München ( HZM ), University of Otago, University of Greifswald, University College of London [London] ( UCL ), National Institute for Health and Welfare, Queen's University [Belfast] ( QUB ), University of Hawaii at Manoa ( UHM ), University of Gothenburg ( GU ) -Institute of Medicine, Recherches en Psychopathologie, nouveaux symptômes et lien social ( EA 4050 ), Université de Poitiers-Université de Brest ( UBO ) -Université Catholique de l'Ouest-Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Finland Institute for Molecular Medicine ( FIMM ), Georgia Prevention Institute, Netherlands Consortium for Healthy Aging, Helmholtz-Zentrum München ( HZM ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Massachusetts General Hospital, Children's Hospital, Boston, Broad Institute, Cambridge, MA, The University of North Carolina at Chapel Hill-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Shungin D, Winkler TW, Adipogen, Consortium, Cardiogramplusc4d, Consortium, Ckdgen, Consortium, Gefos, Consortium, Genie, Consortium, Glgc, Icbp, International, Endogene Consortium, Lifelines, Cohort Study, Magic, Investigator, Muther, Consortium, Consortium, Page, ReproGen Consortium, Amouyel P, D'Adamo, ADAMO PIO, Gasparini, Paolo, Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Hypponen, Elina, Mohlke, Karen L, ADIPOGEN Consortium, Int Endogene Consortium, Lee Kong Chian School of Medicine (LKCMedicine), Epidemiologie, RS: CARIM - R3.02 - Hypertension and target organ damage, Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Olsson, C, Perry, J, Reinmaa, E, Salem, R, Sandholm, N, Schadt, E, Scott, R, Stolk, L, Vallejo, E, Westra, H, Zondervan, K, Amouyel, P, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Brown, M, Burnier, M, Campbell, H, Chakravarti, A, Chines, P, Claudi Boehm, S, Collins, F, Crawford, D, Danesh, J, De Faire, U, De Geus, E, Dörr, M, Erbel, R, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gieger, C, Gudnason, V, Haiman, C, Harris, T, Hattersley, A, Heliövaara, M, Hicks, A, Hingorani, A, Hoffmann, W, Hofman, A, Homuth, G, Humphries, S, Hyppönen, E, Illig, T, Jarvelin, M, Johansen, B, Jousilahti, P, Jula, A, Kaprio, J, Kee, F, Keinanen Kiukaanniemi, S, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lyssenko, V, Männistö, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Musk, A, Möhlenkamp, S, Morris, A, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Palmer, L, Penninx, B, Peters, A, Pramstaller, P, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Shuldiner, A, Staessen, J, Steinthorsdottir, V, Stolk, R, Strauch, K, Tönjes, A, Tremblay, A, Tremoli, E, Vohl, M, Völker, U, Vollenweider, P, Wilson, J, Witteman, J, Adair, L, Bochud, M, Boehm, B, Bornstein, S, Bouchard, C, Cauchi, S, Caulfield, M, Chambers, J, Chasman, D, Cooper, R, Dedoussis, G, Ferrucci, L, Froguel, P, Grabe, H, Hamsten, A, Hui, J, Hveem, K, Jöckel, K, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, März, W, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Pe'Russe, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sinisalo, J, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Van Der Harst, P, Veronesi, G, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Abecasis, G, Assimes, T, Berndt, S, Boehnke, M, Borecki, I, Deloukas, P, Franke, L, Frayling, T, Groop, L, Hunter, D, Kaplan, R, O'Connell, J, Qi, L, Schlessinger, D, Strachan, D, Stefansson, K, Van Duijn, C, Willer, C, Visscher, P, Yang, J, Hirschhorn, J, Zillikens, M, Mccarthy, M, Speliotes, E, North, K, Fox, C, Barroso, I, Franks, P, Ingelsson, E, Heid, I, Loos, R, Cupples, L, Lindgren, C, Mohlke, K, Dastani, Z, Timpson, N, Yuan, X, Henneman, P, Kizer, J, Lyytikainen, L, Fuchsberger, C, Small, K, Coassin, S, Lohman, K, Pankow, J, Uh, H, Wu, Y, Bidulescu, A, Rasmussen Torvik, L, Greenwood, C, Ladouceur, M, Grimsby, J, Manning, A, Mooser, V, Kapur, K, Frants, R, Willemsvan vanDijk, K, Willems, S, Psaty, B, Tracy, R, Brody, J, Chen, I, Viikari, J, Kähönen, M, Evans, D, St Pourcain, B, Sattar, N, Carlson, O, Egan, J, van Heemst, D, Kedenko, L, Nuotio, M, Loo, B, Kanaya, A, Haun, M, Klopp, N, Katsareli, E, Couper, D, Duncan, B, Kloppenburg, M, Borja, J, Musani, S, Guo, X, Semple, R, Teslovich, T, Allison, M, Redline, S, Buxbaum, S, Meulenbelt, I, Ballantyne, C, Hu, F, Paulweber, B, Florez, J, Smith, G, Siscovick, D, Kronenberg, F, van Duijn, C, Waterworth, D, Meigs, J, Dupuis, J, Richards, J, Willenborg, C, Thompson, J, Erdmann, J, Goldstein, B, König, I, Cazier, J, Johansson, Å, Hall, A, Lee, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikäinen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Cox, D, Dimitriou, M, Do, R, El Mokhtari, N, Fontanillas, P, Hager, J, Han, B, Kang, H, Kessler, T, Knowles, J, Kolovou, G, Langford, C, Lokki, M, Lundmark, A, Meisinger, C, Melander, O, Maouche, S, Nikus, K, Peden, J, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Stewart, A, Tan, S, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Basart, H, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, de Faire, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Goodall, A, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kim, H, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Nieminen, M, Hengstenberg, C, Sandhu, M, Pastinen, T, Hovingh, G, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Kathiresan, S, Roberts, R, Schunkert, H, Pattaro, C, Köttgen, A, Garnaas, M, Böger, C, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Döring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Wright, A, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Kroemer, H, Nauck, M, Stracke, S, Völzke, H, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, J, Ruggiero, D, Bergmann, S, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Robino, A, Giulianini, F, Krämer, B, Portas, L, Ford, I, Buckley, B, Adam, M, Thun, G, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, S, Gasparini, P, Pirastu, M, Jukema, J, Probst Hensch, N, Toniolo, D, Coresh, J, Schmidt, R, Kardia, S, Curhan, G, Gyllensten, U, Franke, A, Rettig, R, Parsa, A, Goessling, W, Kao, W, de Boer, I, Peralta, C, Akylbekova, E, Kramer, H, van der Harst, P, Arking, D, Franceschini, N, Hernandez, D, Townsend, R, Lumley, T, Kestenbaum, B, Haritunians, T, Waeber, G, Lu, X, Leak, T, Aasarød, K, Skorpen, F, Baumert, J, Devuyst, O, Mychaleckyj, J, Hallan, S, Navis, G, Shlipak, M, Bull, S, Paterson, A, Rotter, J, Beckmann, J, Dreisbach, A, Styrkarsdottir, U, Evangelou, E, Hsu, Y, Duncan, E, Ntzani, E, Oei, L, Albagha, O, Kemp, J, Koller, D, Minster, R, Vandenput, L, Willner, D, Xiao, S, Yerges Armstrong, L, Zheng, H, Alonso, N, Kammerer, C, Kaptoge, S, Leo, P, Wilson, S, Aalto, V, Alen, M, Aragaki, A, Center, J, Dailiana, Z, Duggan, D, Garcia Giralt, N, Giroux, S, Hocking, L, Husted, L, Jameson, K, Khusainova, R, Kim, G, Koromila, T, Kruk, M, Laaksonen, M, Lacroix, A, Lee, S, Leung, P, Lewis, J, Masi, L, Mencej Bedrac, S, Nguyen, T, Nogues, X, Patel, M, Prezelj, J, Scollen, S, Siggeirsdottir, K, Svensson, O, Trummer, O, van Schoor, N, Woo, J, Zhu, K, Balcells, S, Brandi, M, Cheng, S, Christiansen, C, Cooper, C, Frost, M, Goltzman, D, González Macías, J, Karlsson, M, Khusnutdinova, E, Koh, J, Kollia, P, Langdahl, B, Leslie, W, Lips, P, Ljunggren, Ö, Lorenc, R, Marc, J, Mellström, D, Obermayer Pietsch, B, Olmos, J, Pettersson Kymmer, U, Reid, D, Riancho, J, Rousseau, F, Tang, N, Urreizti, R, Van Hul, W, Zarrabeitia, M, Castano Betancourt, M, Herrera, L, Ingvarsson, T, Johannsdottir, H, Kwan, T, Li, R, Luben, R, Medina Gómez, C, Palsson, S, Reppe, S, Sigurdsson, G, van Meurs, J, Verlaan, D, Williams, F, Zhou, Y, Gautvik, K, Raychaudhuri, S, Cauley, J, Clark, G, Cummings, S, Danoy, P, Dennison, E, Eastell, R, Eisman, J, Jackson, R, Jones, G, Khaw, K, Mccloskey, E, Nandakumar, K, Peacock, M, Pols, H, Prince, R, Reid, I, Robbins, J, Sambrook, P, Sham, P, Tylavsky, F, Econs, M, Kung, A, Reeve, J, Streeten, E, Karasik, D, Ralston, S, Ioannidis, J, Kiel, D, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Mäkinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkilä, O, Hietala, K, Kytö, J, Lahermo, P, Lehto, M, Österholm, A, Parkkonen, M, Pitkäniemi, J, Rosengård Bärlund, M, Saraheimo, M, Sarti, C, Söderlund, J, Soro Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Wadén, J, Gill, G, Prior, S, Guiducci, C, Mirel, D, Taylor, A, Hosseini, M, Parving, H, Rossing, P, Tarnow, L, Ladenvall, C, Alhenc Gelas, F, Lefebvre, P, Rigalleau, V, Roussel, R, Tregouet, D, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Möllsten, A, Cimponeriu, D, Mihai, I, Mota, M, Mota, E, Serafinceanu, C, Stavarachi, M, Hanson, R, Nelson, R, Kretzler, M, Panduru, N, Gu, H, Brismar, K, Zerbini, G, Hadjadj, S, Marre, M, Lajer, M, Waggott, D, Savage, D, Bain, S, Martin, F, Godson, C, Groop, P, Maxwell, A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Fraser, R, Freitag, D, Gurdasani, D, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Van den Herik, E, Volcik, K, Asiki, G, Been, L, Bolton, J, Bonnycastle, L, Burnett, M, Cesana, G, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Kastelein, J, Kim, E, Komulainen, P, Lin, S, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Stančáková, A, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Willemsen, G, Young, E, Bennett, F, Boomsma, D, Bovet, P, Chen, Y, Feranil, A, Freimer, N, Hsiung, C, Järvelin, M, Kesäniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Martin, N, Meneton, P, Moilanen, L, Njølstad, I, Price, J, Sanghera, D, Sheu, W, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Rich, S, Johnson, L, Larson, M, Levy, D, Newton Cheh, C, O'Reilly, P, Palmas, W, Rice, K, Snider, H, Tobin, M, Verwoert, G, Pihur, V, Heath, S, Sõber, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjögren, M, Vinay, D, Alexander, M, Tabara, Y, Shaw Hawkins, S, Whincup, P, Shi, G, Seielstad, M, Sim, X, Nguyen, K, Matullo, G, Gaunt, T, Onland Moret, N, Cooper, M, Platou, C, Org, E, Hardy, R, Dahgam, S, Palmen, J, Kuznetsova, T, Uiterwaal, C, Adeyemo, A, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, N, Chang, Y, Steinle, N, Grobbee, D, Morrison, A, Najjar, S, Hadley, D, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Grässler, J, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Wang, T, Burton, P, Artigas, M, Dong, Y, Wang, X, Zhu, H, Rudock, M, Heckbert, S, Smith, N, Wiggins, K, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, C, Rosengren, A, Thelle, D, Corsi, A, Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Stanèáková, A, Raffel, L, Yao, J, Schwartz, S, Ikram, M, Longstreth W., J, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Morken, M, Laitinen, J, Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Würtz, P, Ong, R, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Dominiczak, A, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Anderson, C, Gordon, S, Guo, Q, Henders, A, Lambert, A, Kraft, P, Kennedy, S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Alizadeh, B, de Boer, R, Boezen, H, van der Klauw, M, Ormel, J, Postma, D, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Lecoeur, C, Johnson, P, Hottenga, J, Salo, P, Bielak, L, Zhao, W, Horikoshi, M, Navarro, P, Chen, H, Rybin, D, Song, K, An, P, Marullo, L, Jansen, H, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Toenjes, A, Peyser, P, Körner, A, Cucca, F, Balkau, B, Bouatia Naji, N, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Hedman, Å, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Higashio, J, Williams, R, Nato, A, Ambite, J, Manolio, T, Hindorff, L, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown Gentry, K, Thornton Wells, T, Dumitrescu, L, Jeff, J, Bush, W, Mitchell, S, Goodloe, R, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Zheng, W, Spencer, K, Pendergrass, S, Wilkens, L, Park, L, Tiirikainen, M, Kolonel, L, Lim, U, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Schumacher, F, Anderson, G, Carlson, C, Prentice, R, Wu, C, Carty, C, Gong, J, Rosse, S, Young, A, Haessler, J, Kocarnik, J, Lin, Y, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chanock, S, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hall, P, Hankinson, S, Hass, M, Heath, A, Janssens, A, Keyzer, J, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Medland, S, Melzer, D, Newman, A, Paré, G, Peeters, P, Pop, V, Räikkönen, K, Salumets, A, Smith, J, Stacey, S, Starr, J, Stathopoulou, M, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Wallaschofski, H, Widen, E, Wijnands van Gent, C, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Feenstra, B, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Easton, D, Foroud, T, Geller, F, Kilpeläinen, T, Li, S, Melbye, M, Murray, J, Murray, S, Ness, A, Northstone, K, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segrè, A, Sovio, U, Srinivasan, S, Tammesoo, M, Tyrer, J, Weedon, M, Young, L, Bierut, L, Boyd, H, Psychiatry, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes
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Adipose Tissue/metabolism ,Male ,genetic association ,subcutaneous fat ,Transcription, Genetic ,Adipocytes ,Adipogenesis ,Adipose Tissue ,Age Factors ,Body Mass Index ,Continental Population Groups ,Epigenesis, Genetic ,Europe ,Female ,Genome, Human ,Humans ,Insulin ,Insulin Resistance ,Models, Biological ,Neovascularization, Physiologic ,Obesity ,Polymorphism, Single Nucleotide ,Quantitative Trait Loci ,Sex Characteristics ,Waist-Hip Ratio ,Body Fat Distribution ,Genome-Wide Association Study ,Multidisciplinary ,Insulin Resistance/genetics ,Genome-wide association study ,Continental Population Groups/genetics ,genetic analysis ,heritability ,gene cluster ,Science::Biological sciences::Human anatomy and physiology [DRNTU] ,0302 clinical medicine ,high density lipoprotein cholesterol ,Models ,genetics [Insulin Resistance] ,histone modification ,Age Factor ,insulin receptor ,0303 health sciences ,Adipocyte ,Human/genetics ,CARDIOGRAMplusC4D Consortium ,ADIPOGENIC DIFFERENTIATION ,genetic correlation ,body fat ,Continental Population Group ,priority journal ,5 trisphosphate 3 phosphatase ,GEFOS Consortium ,meta analysis (topic) ,Science & Technology - Other Topics ,ddc:500 ,transcription regulation ,Adipogenesis/genetics ,Single Nucleotide/genetics ,Human ,medicine.medical_specialty ,Waist ,phosphatidylinositol 3 ,European ,ta3111 ,genetic regulation ,Article ,developmental biology ,03 medical and health sciences ,MAGIC Investigators ,transcription initiation site ,SDG 3 - Good Health and Well-being ,Genetic ,genomics ,GLYCEMIC TRAITS ,genetics [Continental Population Groups] ,Polymorphism ,GENOME-WIDE ASSOCIATION ,Physiologic ,genetics [Adipogenesis] ,Adipocytes/metabolism ,Europe/ethnology ,Genome, Human/genetics ,Insulin/metabolism ,Neovascularization, Physiologic/genetics ,Obesity/genetics ,Polymorphism, Single Nucleotide/genetics ,Quantitative Trait Loci/genetics ,Transcription, Genetic/genetics ,Genetic/genetics ,Adipogenesi ,Science & Technology ,adiponectin ,[ SDV ] Life Sciences [q-bio] ,vasculotropin ,genetics [Quantitative Trait Loci] ,ta1184 ,Racial Groups ,ta1182 ,gene mapping ,ta3121 ,triacylglycerol blood level ,medicine.disease ,Biological ,major clinical study ,amino acid sequence ,metabolism [Insulin] ,Endocrinology ,metabolism [Adipocytes] ,genetic loci, insulin, body fat ,GLGC ,International Endogene Consortium ,metabolism [Adipose Tissue] ,Body mass index ,HUMAN HEIGHT ,Epigenesis ,LifeLines Cohort Study ,ReproGen Consortium ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,tissue level ,Physiologic/genetics ,[SDV]Life Sciences [q-bio] ,Medizin ,Adipose tissue ,low density lipoprotein cholesterol ,PAGE Consortium ,COMMON SNPS ,angiogenesis ,Waist–hip ratio ,genetics [Obesity] ,MESH: Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio ,single nucleotide polymorphism ,fat ,genetic variability ,molecular biology ,body mass index (BMI) ,ethnology [Europe] ,peroxisome proliferator activated receptor ,2. Zero hunger ,Genetics ,Genome ,Single Nucleotide ,waist circumference ,insulin ,phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase ,triacylglycerol ,vasculotropin, developmental biology ,gene expression ,genome ,numerical model, adipocyte ,adipose tissue ,body fat distribution ,body mass ,female ,gene locus ,gene structure ,hip circumference ,human ,insulin resistance ,lipoprotein blood level ,male ,obesity ,protein protein interaction ,sex difference ,waist hip ratio ,Multidisciplinary Sciences ,genetics [Transcription, Genetic] ,genetics [Polymorphism, Single Nucleotide] ,ADIPOGen Consortium ,genetics [Neovascularization, Physiologic] ,Transcription ,SUSCEPTIBILITY LOCI ,General Science & Technology ,ICBP ,030209 endocrinology & metabolism ,Biology ,adipocyte ,MESH : Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio ,MESENCHYMAL STEM-CELLS ,GENIE Consortium ,SEXUAL-DIMORPHISM ,Insulin resistance ,Internal medicine ,medicine ,genetics [Genome, Human] ,ABDOMINAL ADIPOSITY ,Neovascularization ,030304 developmental biology ,FALSE DISCOVERY ,CKDGen Consortium ,Sex Characteristic ,MuTHER Consortium ,numerical model - Abstract
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P
- Published
- 2015
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36. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study
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Winkler, Thomas W, Justice, Anne E, Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F, Chu, Su, Czajkowski, Jacek, Esko, Tõnu, Fall, Tove, Kilpeläinen, Tuomas O, Lu, Yingchang, Mägi, Reedik, Mihailov, Evelin, Pers, Tune H, Rüeger, Sina, Teumer, Alexander, Ehret, Georg B, Ferreira, Teresa, Heard-Costa, Nancy L, Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D, Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M, Jansen, Rick, Westra, Harm-Jan, White, Charles C, Absher, Devin, Ahluwalia, Tarunveer S, Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L, de Craen, Anton JM, Bis, Joshua C, Bonnefond, Amélie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston WK, Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E, Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B, Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E, Jackson, Anne U, Jacobs, Kevin B, Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E, Lahti, Jari, Mateo Leach, Irene, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela AF, Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L, Montasser, May E, Müller, Gabriele, Müller-Nurasyid, Martina, Nolte, Ilja M, Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W, Renström, Frida, Rizzi, Federica, Rose, Lynda M, Ryan, Kathy A, Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stančáková, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J, Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P, Vandenput, Liesbeth, van der Laan, Sander W, van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V, Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L, Wang, Sophie R, Wang, Zhaoming, Wild, Sarah H, Willenborg, Christina, Wilson, James F, Wong, Andrew, Yang, Jian, Yengo, Loïc, Yerges-Armstrong, Laura M, Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A, Bakker, Stephan JL, Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blüher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L, Boyd, Heather A, Bruinenberg, Marcel, Buchman, Aron S, Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S, Claudi-Boehm, Simone, Cole, John, Collins, Francis S, de Geus, Eco JC, de Groot, Lisette CPGM, Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G, Friedrich, Nele, Gejman, Pablo V, Gigante, Bruna, Glorioso, Nicola, Go, Alan S, Gottesman, Omri, Gräßler, Jürgen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T, Heath, Andrew C, Henders, Anjali K, Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G, Hui, Jennie, Husemoen, Lise L, Hutri-Kähönen, Nina, Hysi, Pirro G, Illig, Thomas, De Jager, Philip L, Jalilzadeh, Shapour, Jørgensen, Torben, Jukema, J Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J, Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T, Kratzer, Wolfgang, Krüger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J, Leander, Karin, Lindström, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stéphane, Luben, Robert, Lyssenko, Valeriya, Männistö, Satu, Magnusson, Patrik K, McArdle, Wendy L, Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W, Morris, Andrew P, Narisu, Narisu, Nelis, Mari, Ong, Ken K, Palotie, Aarno, Pérusse, Louis, Pichler, Irene, Pilia, Maria G, Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M, Rice, Treva K, Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R, Sarzynski, Mark A, Scholtens, Salome, Scott, Robert A, Scott, William R, Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P Eline, Smit, Jan H, Sparsø, Thomas H, Stirrups, Kathleen, Stolk, Ronald P, Stringham, Heather M, Swertz, Morris A, Swift, Amy J, Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J, Völker, Uwe, Vohl, Marie-Claude, Vonk, Judith M, Waldenberger, Melanie, Walker, Ryan W, Wennauer, Roman, Widén, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F, Zillikens, M Carola, van Dijk, Suzanne C, van Schoor, Natasja M, Asselbergs, Folkert W, de Bakker, Paul IW, Beckmann, Jacques S, Beilby, John, Bennett, David 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Nicholas G, Laakso, Markku, Lakka, Timo A, Lehtimäki, Terho, Lettre, Guillaume, Levinson, Douglas F, Lind, Lars, Lokki, Marja-Liisa, Mäntyselkä, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D, Moll, Frans L, Murray, Jeffrey C, Musk, Arthur W, Nieminen, Markku S, Njølstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J, Oostra, Ben A, Palmer, Lyle J, Pankow, James S, Pasterkamp, Gerard, Pedersen, Nancy L, Pedersen, Oluf, Penninx, Brenda W, Perola, Markus, Peters, Annette, Polašek, Ozren, Pramstaller, Peter P, Psaty, Bruce M, Qi, Lu, Quertermous, Thomas, Raitakari, Olli T, Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M, Rioux, John D, Rivadeneira, Fernando, Rotter, Jerome I, Rudan, Igor, den Ruijter, Hester M, Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter EH, Shuldiner, Alan R, Sinisalo, Juha, Snieder, Harold, Sørensen, Thorkild IA, Spector, Tim D, Staessen, Jan A, Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, André G, Uusitupa, Matti, Verbeek, André LM, Vermeulen, Sita H, Viikari, Jorma S, Vitart, Veronique, Völzke, Henry, Vollenweider, Peter, Waeber, Gérard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J, Watkins, Hugh, Zeggini, Eleftheria, arcOGEN Consortium, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Chakravarti, Aravinda, Clegg, Deborah J, Cupples, L Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E, Rao, DC, Abecasis, Goncalo R, Assimes, Themistocles L, Barroso, Inês, Berndt, Sonja I, Boehnke, Michael, Deloukas, Panos, Fox, Caroline S, Groop, Leif C, Hunter, David J, Ingelsson, Erik, Kaplan, Robert C, McCarthy, Mark I, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Hirschhorn, Joel N, Lindgren, Cecilia M, Heid, Iris M, North, Kari E, Borecki, Ingrid B, Kutalik, Zoltán, Loos, Ruth JF, Division of Statistical Genomics, Washington University School of Medicine, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Estonian Genome and Medicine, University of Tartu, Institute of Molecular and Cell Biology, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Metabolic Science, MRC, Brown University, Center for Biological Sequence Analysis [Lyngby], Technical University of Denmark [Lyngby] (DTU), King‘s College London, Groningen Bioinformatics Centre, GBB, University of Groningen [Groningen], University of Queensland [Brisbane], National Institut of Food Science and Technology, University of Agriculture, Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of neurology, Leiden University Medical Center (LUMC), University of Washington [Seattle], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Deptartment of Medical Biochemistry and Microbiology, Uppsala University, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Limnology, Ecology, Department of Ecology and Evolutionary Biology, University of California, Core Genotyping Facility, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Division of Cancer Epidemiology and Genetics, Institute of Health Sciences and Biocenter Oulu, University of Oulu, Department of Chemical Engineering Taiwan (DCET - NTHU), National Tsing Hua University [Hsinchu] (NTHU), University of Oxford [Oxford], Department of Epidemiology, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], Departments of Epidemiology and Nutrition, Harvard School of Public Health, Department of Clinical Sciences, Lund University [Lund]-Lund University Diabetes Centre, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Department of Medical Sciences, Department of Educational Psychology and Counseling, National Taiwan Normal University (NTNU), Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE Genetics, deCODE genetics [Reykjavik], Interuniversity Cardiology Institute Netherlands, Molecular Genetics Section, University of Groningen [Groningen]-University Medical Centre Groningen, Kidney Center, University Medical Center Groningen [Groningen] (UMCG), The University of Texas Health Science Center at Houston (UTHealth), Texas Biomedical Research Institute [San Antonio, TX], Medical Department III, Universität Leipzig [Leipzig], Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], GNS Science, Blackett Laboratory, Imperial College London, Medstar Research Institute, University of Rochester [USA], MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Dept Biochem & Mol Biol, Pennsylvania State University (Penn State), Penn State System-Penn State System, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Epidemiology, University Medical Centre Groningen, Unit for Molecular Epidemiology, German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Research Centre for Prevention and Health (RCPH), Department of Public Health [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Capital Region of Denmark, University of Copenhagen = Københavns Universitet (KU), Faculty of Medicine, Institute of Public Health, Aalborg University [Denmark] (AAU), Department of Nutrition-Dietetics, Harokopio University of Athens, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, MRC National Survey of Health and Development, MRC Unit for Lifelong Health and Ageing, Department of Epidemiology and Public Health, University College of London [London] (UCL), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Research Center for Prevention and Health, Glostrup Hospital, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Cambridge Institute of Public Health, University of Cambridge [UK] (CAM), Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Queensland Institute of Medical Research, Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Head of Medical Sequencing, Department of Biostatistics, University of Washington, Department of Chronic Disease Prevention, Molecular Epidemiology, Department of Genetics, Université Laval [Québec] (ULaval), Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Department of Internal Medicine, Université de Lausanne (UNIL), Carl Gustav Carus University Hospital, Loughborough University, Genomics and Bioinformatics Platform, Fondazione Filarete, Department of Medicine, Surgery, and Dentistry, University of Milano, Medizinische Klinik II, Universität zu Lübeck [Lübeck], Department of Genomic Medicine, University of Manchester [Manchester], The Wellcome Trust Centre for Human Genetics [Oxford], National Institutes of Health [Bethesda] (NIH), Department of Nephrology, University Medical Center, University of Groningen, Helmholtz-Zentrum München (HZM), Icelandic Heart Association, Kopavogur, Iceland., Faculty of Medicine, University of Iceland [Reykjavik], Genetics and Pathology, Department of child and adolescent psychiatry, Universität Duisburg-Essen [Essen], Department of Internal Medicine II, Division of Respirology, University of Regensburg, Regensburg, Germany, Universität Regensburg (UR), Franz-Volhard-Centrum für Klinische Forschung, ECRC, Department of Clinical Physiology, University of Tampere [Finland]-Tampere University Hospital, Finnish Institute of Occupational Health of Helsinki, Department of Clinical Chemistry, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Department of Oncology, University of Tampere Medical School, University of Tampere, Department of Physiology, University of Eastern Finland-Institute of Biomedicine, Department of Medicine, Montreal, Developmental Brain and Behaviour Unit, University of Southampton, Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, Centre for Bone and Arthritis Research, Institute of Medicine-University of Gothenburg (GU), Interdisciplinary Center for Psychiatric Epidemiology, Experimental Cardiology Laboratory, University Medical Center [Utrecht], Peter MacCallum Cancer Center, Faculty of Health Sciences, Aarhus University [Aarhus], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Department of Health Services, University of Washington, Group Health Research Institute, Group Health Cooperative, Department of Epidemiology, University of Washington, Department of Medicine, University of Washington, Cardiovascular Health Research Unit, University of Washington, The Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku University Hospital (TYKS), Erasmus Medical Centre, Cedars-Sinai Medical Center, Department of Pathological Biochemistry, Royal Infirmary, Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Department of Pediatrics, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Institute of Preventive Medicine, Copenhagen University Hospital-Bispebjerg and Frederiksberg Hospitals, Maastricht University [Maastricht], Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Department of Epidemiology & Biostatistics, Radboud University Medical Center [Nijmegen], Institute for Community Medicine, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), MRC epidemiology Unit, Framingham Heart Study, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Metabolic Disease Group, University of Cambridge Metabolic Research Laboratories, Department of Genetics and Biotechnology, Wellcome Trust, Divisions of Genetics and Endocrinology and Program in Genomics, Boston Children's Hospital, Metabolism Initiative and Program in Medical and Population Genetics, Endocrinology and Metabolism, The Churchill Hospital-Oxford Centre for Diabetes, Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Department of Medical Genetics, Epidemiology Unit, Addenbrooke's Hospital-Medical Research Council (MRC), P30 AG010161/AG/NIA NIH HHS/United States, Psychiatry, Epidemiology and Data Science, NCA - Neurobiology of mental health, EMGO - Lifestyle, overweight and diabetes, APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Other departments, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, RS: CARIM - R3 - Vascular biology, MUMC+: DA BV AIOS Radiologie (9), Epidemiologie, Orthopedie, Institute for Molecular Medicine Finland, Helsinki Collegium for Advanced Studies, Behavioural Sciences, University of Helsinki, Transplantation Laboratory, Medicum, Research Programs Unit, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Children's Hospital, Lastentautien yksikkö, Marja-Liisa Lokki / Principal Investigator, Kardiologian yksikkö, Leif Groop Research Group, Quantitative Genetics, Developmental Psychology Research Group, Genomics of Neurological and Neuropsychiatric Disorders, Genomic Discoveries and Clinical Translation, Ehret, Georg Benedikt, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Universiteit Leiden-Universiteit Leiden, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), University of California (UC), University of Oxford, Lund University [Lund], Universität Leipzig, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Capital Region of Denmark, University of Copenhagen = Københavns Universitet (UCPH), Université de Lausanne = University of Lausanne (UNIL), Universität zu Lübeck = University of Lübeck [Lübeck], Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Gothenburg (GU)-Institute of Medicine, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Luan, Jian'an [0000-0003-3137-6337], Tyrer, Jonathan [0000-0003-3724-4757], Forouhi, Nita [0000-0002-5041-248X], Khaw, Kay-Tee [0000-0002-8802-2903], Langenberg, Claudia [0000-0002-5017-7344], Luben, Robert [0000-0002-5088-6343], Ong, Kenneth [0000-0003-4689-7530], Johnson, Kathleen [0000-0002-6823-3252], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Apollo - University of Cambridge Repository, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Biochemistry, Surgery, Internal Medicine, Public Health, Medical Oncology, Pathology, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, and Clinical Genetics
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0301 basic medicine ,Netherlands Twin Register (NTR) ,Male ,Cancer Research ,endocrine system diseases ,Biological pathways ,QH426-470 ,Genome ,Body Mass Index ,Body Size ,Genetics (clinical) ,ddc:616 ,Genetics & Heredity ,Sex Characteristics ,Loci ,MAGIC Consortium ,Mass index ,Age Factors ,Chromosome Mapping ,Middle Aged ,Genealogy ,Self-reported height ,Peripheral-blood ,Scale (social sciences) ,ICBP Consortium ,Female ,Life Sciences & Biomedicine ,Medical Genetics ,Research Article ,arcOGEN Consortium ,musculoskeletal diseases ,Adult ,European Continental Ancestry Group ,Natural menopause ,Aged ,Body Size/genetics ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Polymorphism, Single Nucleotide ,Waist-Hip Ratio ,Biology ,Body size ,DIAGRAM Consortium ,Age and sex ,White People ,Fat distribution ,GLGC Consortium ,03 medical and health sciences ,Life-course ,Genetics ,Weight-gain ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Medicinsk genetik ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,0604 Genetics ,Science & Technology ,nutritional and metabolic diseases ,Correction ,030104 developmental biology ,GWAS meta-analysis ,Global-BPGen Consortium ,Common SNPS ,CHARGE Consortium ,3111 Biomedicine ,Developmental Biology - Abstract
Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR, Author Summary Adult body size and body shape differ substantially between men and women and change over time. More than 100 genetic variants that influence body mass index (measure of body size) or waist-to-hip ratio (measure of body shape) have been identified. While there is evidence that some genetic loci affect body shape differently in men than in women, little is known about whether genetic effects differ in older compared to younger adults, and whether such changes differ between men and women. Therefore, we conducted a systematic genome-wide search, including 114 studies (>320,000 individuals), to specifically identify genetic loci with age- and or sex-dependent effects on body size and shape. We identified 15 loci of which the effect on BMI was different in older compared to younger adults, whereas we found no evidence for loci with different effects in men compared to women. The opposite was seen for body shape as we identified 44 loci of which the effect on waist-to-hip ratio differed between men and women, but no difference between younger and older adults were observed. Our observations may provide new insights into the biology that underlies weight change with age or the sexual dimorphism of body shape.
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- 2014
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37. Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014
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Gael Darren Maganga, Magassouba N’Faly, Martin Gabriel, Augustine Goba, Sunday Omilabu, Eric M. Leroy, J. Rodney Brister, Stephen K. Gire, Jens H. Kuhn, Nathan L. Yozwiak, Placide Mbala, Rachel Sealfon, Lina M. Moses, Jeffrey R. Kugelman, Kristian G. Andersen, Olga Blinkova, Christian T. Happi, Jimmy Kapetshi, Peter B. Jahrling, P. Formenty, Nicolas Berthet, Cynthia A. Rossi, Yīmíng Bào, Joseph N. Fair, John S. Schieffelin, Jonathan S. Towner, Gustavo Palacios, Robert Swanepoel, Robert F. Garry, Daniel Park, Janusz T. Paweska, Jiro Wada, Anna N. Clawson, Gary Kobinger, Sylvain Baize, Nadia Wauquier, Jean-Paul Gonzalez, Sina Bavari, Stuart T. Nichol, Randal J. Schoepp, Sheli R. Radoshitzky, Stephan Günther, Jean-Jacques Muyembe-Tamfum, Pardis C. Sabeti, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), FAS Center for Systems Biology, Harvard University, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), National Center for Biotechnology Information (NCBI), U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Centre International de Recherches Médicales de Franceville (CIRMF), Fondation Mérieux, Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany] (BNITM), German Center for Infection Research, Partnersite Munich (DZIF), Tulane University, Harvard FAS Center for Systems Biologyy, Kenema Government Hospital, Metabiota Inc. [San Francisco], Redeemer's University [Lagos, Nigeria], Institut National de Recherche Biomédicale [Kinshasa] (INRB), Special Pathogens Programme, National Microbiology Laboratory, Public Health Agency of Canada, Université Gamal Abdel Nasser de Conakry, Laboratoire des Fièvres Hémorragiques en Guinée, Donka National Hospital, Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Department of Medical Microbiology and Parasitology, College of Medicine, University of Lagos, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), National Institute for Communicable Diseases [Johannesburg] (NICD), Computer Science and Artificial Intelligence Laboratory [Cambridge] (CSAIL), Massachusetts Institute of Technology (MIT), University of Pretoria [South Africa], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Harvard University [Cambridge], Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], U.S. Army Medical Research Institute of Infectious Diseases, and Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge]
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virus strain ,MESH: Sequence Analysis, DNA ,Letter ,genome annotation ,lcsh:QR1-502 ,Filoviridae ,virus nomenclature ,medicine.disease_cause ,lcsh:Microbiology ,Disease Outbreaks ,West africa ,virus variant ,Ebola virus ,Makona ,Lokolia ,MESH: Disease Outbreaks ,Mononegavirales ,virus classification ,MESH: Phylogeny ,Nomenclature ,Phylogeny ,MESH: Guinea ,biology ,3. Good health ,Lomela ,Infectious Diseases ,MESH: RNA, Viral ,Ebola ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Democratic Republic of the Congo ,RNA, Viral ,filovirus ,MESH: Terminology as Topic ,filovirid ,virus taxonomy ,Terminology as Topic ,Virology ,medicine ,Humans ,virus isolate ,MESH: Ebolavirus ,Virus classification ,ebolavirus ,Ebolavirus ,mononegavirus ,MESH: Humans ,mononegavirad ,Outbreak ,Sequence Analysis, DNA ,MESH: Democratic Republic of the Congo ,Hemorrhagic Fever, Ebola ,biology.organism_classification ,MESH: Hemorrhagic Fever, Ebola ,Guinea - Abstract
International audience; In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: "Makona", Middle Africa: "Lomela") and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures.
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- 2014
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38. Maximizing the Power of Principal-Component Analysis of Correlated Phenotypes in Genome-wide Association Studies
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Peter Kraft, Nicolas Greliche, Hugues Aschard, Pierre-Emmanuel Morange, Bjarni J. Vilhjálmsson, David-Alexandre Trégouët, Harvard School of Public Health, Broad Institute [Cambridge], Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Program in Genetic Epidemiology and Statistical Genetics (PGESG - BOSTON), Harvard University-Massachusetts Institute of Technology (MIT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
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Multivariate analysis ,Genome-wide association study ,Biology ,MESH: Phenotype ,Polymorphism, Single Nucleotide ,Article ,Correlation ,Quantitative Trait, Heritable ,MESH: Quantitative Trait, Heritable ,Statistics ,Genetics ,Humans ,Genetics(clinical) ,MESH: Models, Genetic ,Genetics (clinical) ,Genetic association ,Venous Thrombosis ,MESH: Principal Component Analysis ,Principal Component Analysis ,[STAT.AP]Statistics [stat]/Applications [stat.AP] ,MESH: Humans ,Models, Genetic ,Dimensionality reduction ,MESH: Polymorphism, Single Nucleotide ,Robustness (evolution) ,Phenotype ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Principal component analysis ,MESH: Genome-Wide Association Study ,MESH: Venous Thrombosis ,Trait ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,[STAT.ME]Statistics [stat]/Methodology [stat.ME] ,Genome-Wide Association Study - Abstract
International audience; Many human traits are highly correlated. This correlation can be leveraged to improve the power of genetic association tests to identify markers associated with one or more of the traits. Principal component analysis (PCA) is a useful tool that has been widely used for the multivariate analysis of correlated variables. PCA is usually applied as a dimension reduction method: the few top principal components (PCs) explaining most of total trait variance are tested for association with a predictor of interest, and the remaining components are not analyzed. In this study we review the theoretical basis of PCA and describe the behavior of PCA when testing for association between a SNP and correlated traits. We then use simulation to compare the power of various PCA-based strategies when analyzing up to 100 correlated traits. We show that contrary to widespread practice, testing only the top PCs often has low power, whereas combining signal across all PCs can have greater power. This power gain is primarily due to increased power to detect genetic variants with opposite effects on positively correlated traits and variants that are exclusively associated with a single trait. Relative to other methods, the combined-PC approach has close to optimal power in all scenarios considered while offering more flexibility and more robustness to potential confounders. Finally, we apply the proposed PCA strategy to the genome-wide association study of five correlated coagulation traits where we identify two candidate SNPs that were not found by the standard approach.
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- 2014
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39. Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species
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Dent Earl, Jacob O. Kitzman, Iain MacCallum, James R. Knight, Jacques Corbeil, Elenie Godzaridis, Cristian Del Fabbro, Paul J. Kersey, Martin Hunt, Octávio S. Paulo, Joseph Fass, Isaac Ho, Michael C. Schatz, Erich D. Jarvis, Dominique Lavenier, Simone Scalabrin, Thomas D. Otto, Nicolas Maillet, Siu-Ming Yiu, Timothy I. Shaw, David B. Jaffe, Henry Song, Ruibang Luo, Steve Goldstein, David Haussler, Francisco Pina-Martins, Richard A. Gibbs, Adam M. Phillippy, Michael Bechner, Ganeshkumar Ganapathy, Stephen Richards, Riccardo Vicedomini, Shuangye Yin, François Laviolette, Yingrui Li, T. Roderick Docking, Binghang Liu, Carson Qu, Wen-Chi Chou, Hao Zhang, Nuno A. Fonseca, Dariusz Przybylski, Bruno Vieira, Yue Liu, Matthew D. MacManes, Sébastien Boisvert, Yujian Shi, Jared T. Simpson, Sergey Kazakov, Sergey Koren, Jarrod Chapman, Giles Hall, Paul Baranay, Sante Gnerre, Shiguo Zhou, Rayan Chikhi, Filipe J. Ribeiro, Jason T. Howard, Zhenyu Li, Pavel Fedotov, Jay Shendure, J. Graham Ruby, Joseph B. Hiatt, Benedict Paten, Ian F Korf, David C. Schwartz, Keith Bradnam, Jianying Yuan, Alexey Sergushichev, Jun Wang, Hamidreza Chitsaz, Daniel S. Rokhsar, Inanc Birol, Huaiyang Jiang, Kim C. Worley, Anton Alexandrov, Zemin Ning, Delphine Naquin, Michael Place, Matthias Haimel, Guojie Zhang, Guillaume Chapuis, Fedor Tsarev, Scott J. Emrich, Shaun D. Jackman, Sergey Melnikov, Xiang Qin, Ted Sharpe, Francesco Vezzi, Tak-Wah Lam, Richard Durbin, Genome Center [UC Davis], University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), National Research University of Information Technologies, Mechanics and Optics [St. Petersburg] (ITMO), Computational Biology and Bioinformatics [New Haven], Yale University [New Haven], Laboratory for Molecular and Computational Genomics [Madison], University of Wisconsin-Madison, Genome Sciences Centre [Vancouver] (GSC), British Columbia Cancer Agency, Infectious Diseases Research Center [Québec], Université Laval [Québec] (ULaval), Faculté de médecine de l'Université Laval [Québec] (ULaval), DOE Joint Genome Institute [Walnut Creek], Biological systems and models, bioinformatics and sequences (SYMBIOSE), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), Dependability Interoperability and perfOrmance aNalYsiS Of networkS (DIONYSOS), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-RÉSEAUX, TÉLÉCOMMUNICATION ET SERVICES (IRISA-D2), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Department of computer science [Detroit], Wayne State University [Detroit], Institute of Bioinformatics [Athens], University of Georgia [USA], Institute of Aging Research [Boston], Hebrew SeniorLife [Boston], Department of Molecular Medicine [Québec], Institute of Applied Genomics [Udine] (IGA), Institute of Applied Genomics, The Wellcome Trust Sanger Institute [Cambridge], Howard Hughes Medical Institute [Santa Cruz] (HHMI), Howard Hughes Medical Institute (HHMI)-University of California [Santa Cruz] (UC Santa Cruz), Department of Computer Science and Engineering [South Bend], University of Notre Dame [Indiana] (UND), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, CRACS & Inesc TEC [Porto], Universidade do Porto = University of Porto, Medical Center [Durham], Duke University [Durham], Human Genome Sequencing Center [Houston] (HGSC), Baylor College of Medicine (BCM), Baylor University-Baylor University, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Faculty of Medicine, Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], 454 Life Sciences [Branford], 454 Life Sciences, National Biodefense Analysis and Countermeasures Center [Frederick], U.S. Social Security Administration, Center for Bioinformatics and Computational Biology [Maryland] (CBCB), University of Maryland [College Park], University of Maryland System-University of Maryland System, HKU-BGI Bioinformatics Algorithms and Core Technology Research Laboratory [Hong Kong], The University of Hong Kong (HKU), Invariant Preserving SOlvers (IPSO), Institut de Recherche Mathématique de Rennes (IRMAR), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Department of Computer Science and Software Engineering [Québec], Beijing Genomics Institute [Shenzhen] (BGI), Berkeley California Institute for Quantitative Biosciences [Berkeley], University of California (UC), Computational Biology & Population Genomics Group [Lisboa], Centre for Environmental Biology, New York Genome Center [New York], New York Genome Center, Department of Molecular and Cell Biology, Department of Biochemistry and Biophysics, Howard Hughes Medical Institute (HHMI), Simons Center for Quantitative Biology [Cold Spring Harbor], Cold Spring Harbor Laboratory, Department of Epidemiology and Biostatistics [Athens], University of Georgia [USA]-College of Public Health, Science for Life Laboratory [Solna], Royal Institute of Technology [Stockholm] (KTH ), Department of Mathematics and Computer Science [Udine], Università degli Studi di Udine - University of Udine [Italie], University of California-University of California, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Howard Hughes Medical Institute (HHMI)-University of California [Santa Cruz] (UCSC), Universidade do Porto, Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-AGROCAMPUS OUEST, Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Inria Rennes – Bretagne Atlantique, and University of California
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[INFO.INFO-AR]Computer Science [cs]/Hardware Architecture [cs.AR] ,Computer science ,Sequence assembly ,GENOMES ,Health Informatics ,Computational biology ,Assessment ,COMPASS ,Genome ,03 medical and health sciences ,0302 clinical medicine ,biology.animal ,Quantitative Biology - Genomics ,Gene ,030304 developmental biology ,Sequence (medicine) ,Scaffolds ,Genomics (q-bio.GN) ,Whole genome sequencing ,0303 health sciences ,Genome assembly ,Heterozygosity ,biology ,N50 ,Research ,Vertebrate ,De novo Assembly ,Computer Science Applications ,Fosmid ,FOS: Biological sciences ,Scalability ,030217 neurology & neurosurgery - Abstract
Background - The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results - In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions - Many current genome assemblers produced useful assemblies, containing a significant representation of their genes, regulatory sequences, and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another., Comment: Additional files available at http://korflab.ucdavis.edu/Datasets/Assemblathon/Assemblathon2/Additional_files/ Major changes 1. Accessions for the 3 read data sets have now been included 2. New file: spreadsheet containing details of all Study, Sample, Run, & Experiment identifiers 3. Made miscellaneous changes to address reviewers comments. DOIs added to GigaDB datasets
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- 2013
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40. Linkage to the mating-type locus across the genus Microbotryum: insights into nonrecombining chromosomes
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Petit, Elsa, Giraud, Tatiana, de Vienne, Damien, Coelho, Marco, Aguileta, Gabriela, Amselem, Joelle, Kreplak, Jonathan, Poulain, Julie, Gavory, Frédérick, Wincker, Patrick, Young, Sarah, Cuomo, Christina, Perlin, Michael, Hood, Michael, Amherst College, Université Paris-Sud - Paris 11 (UP11), Centre for Genomic Regulation [Barcelona] (CRG), Universitat Pompeu Fabra [Barcelona] (UPF)-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Centro de Recursos Microbiológicos-Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Centre for Genomic Regulation (CRG), BIOlogie et GEstion des Risques en agriculture (BIOGER), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Unité de Recherche Génomique Info (URGI), Institut National de la Recherche Agronomique (INRA), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Department of Biology, Program on Disease Evolution, University of Louisville, Department of Biology, NSF [DEB 0747222], 'Consortium National de Recherche en Genomique' of the Museum National d'Histoire Naturelle (CNRS IFR 101), 'service de systematique moleculaire' of the Museum National d'Histoire Naturelle (CNRS IFR 101), National Science Foundation (NSF) [National Science Foundation (NSF) grant 0947963], [ANR-09-0064-01], ANR-09-BLAN-0064,FungiSex,Evolution des types sexuels et des chromosomes sexuels chez les champignons(2009), Stockbridge School of Agriculture, University of Massachusetts System (UMASS), AgroParisTech, Université Paris Saclay (COmUE), Ecologie Systématique et Evolution (ESE), Université Paris-Sud - Paris 11 (UP11)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Bioinformatique, phylogénie et génomique évolutive (BPGE), Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Departamento de Ciencias da Vida (DCV), Faculdade de Ciências e Tecnologia (FCT NOVA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), Agroécologie [Dijon], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Universitat Pompeu Fabra [Barcelona]-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Centre National de la Recherche Scientifique (CNRS)-AgroParisTech-Université Paris-Sud - Paris 11 (UP11), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université de Bourgogne (UB)-Institut National de la Recherche Agronomique (INRA)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, National Science Foundation (NSF) DEB 0747222, National Science Foundation (NSF)National Science Foundation (NSF) grant 094796, and National Science Foundation (NSF)NSF - Directorate for Biological Sciences (BIO) 0947963
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Recombination, Genetic ,mating-type chromosome ,DNA, Complementary ,Polymorphism, Genetic ,gene conversion ,Evolutionary strata ,Genetic Linkage ,[SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] ,[SDV]Life Sciences [q-bio] ,Basidiomycota ,Molecular Sequence Data ,Sequence Analysis, DNA ,Genes, Mating Type, Fungal ,Polymerase Chain Reaction ,recombination ,Receptors, Pheromone ,Evolution, Molecular ,Fungal Proteins ,Species Specificity ,sex chromosome ,DNA, Fungal ,ComputingMilieux_MISCELLANEOUS ,Alleles ,Phylogeny - Abstract
International audience; Parallels have been drawn between the evolution of nonrecombining regions in fungal mating-type chromosomes and animal and plant sex chromosomes, particularly regarding the stages of recombination cessation forming evolutionary strata of allelic divergence. Currently, evidence and explanations for recombination cessation in fungi are sparse, and the presence of evolutionary strata has been examined in a minimal number of fungal taxa. Here, the basidiomycete genus Microbotryum was used to determine the history of recombination cessation for loci on the mating-type chromosomes. Ancestry of linkage with mating type for 13 loci was assessed across 20 species by a phylogenetic method. No locus was found to exhibit trans-specific polymorphism for alternate alleles as old as the mating pheromone receptor, indicating that ages of linkage to mating type varied among the loci. The ordering of loci in the ancestry of linkage to mating type does not agree with their previously proposed assignments to evolutionary strata. This study suggests that processes capable of influencing divergence between alternate alleles may act at loci in the nonrecombining regions (e.g., gene conversion) and encourages further work to dissect the evolutionary processes acting upon genomic regions that determine mating compatibility.
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- 2012
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41. Common variants at 12q14 and 12q24 are associated with hippocampal volume
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Bis, Joshua C, DeCarli, Charles, Schuur, Maaike, Grimm, Oliver, Hollinshead, Marisa, Holmes, Avram J, Homuth, Georg, Hottenga, Jouke-Jan, Langan, Camilla, Lopez, Lorna M, Hansell, Narelle K, Hwang, Kristy S, Kim, Sungeun, Yu, Lei, Laje, Gonzalo, Lee, Phil H, Liu, Xinmin, Loth, Eva, Lourdusamy, Anbarasu, Maniega, Susana Muñoz, Mattingsdal, Morten, Mohnke, Sebastian, Nho, Kwangsik, Nugent, Allison C, Choi, Seung-Hoan, O'Brien, Carol, Papmeyer, Martina, Pütz, Benno, Ramasamy, Adaikalavan, Rasmussen, Jerod, Rijpkema, Mark, Risacher, Shannon L, Roddey, J Cooper, Rose, Emma J, Ryten, Mina, Sigurdsson, Sigurdur, Shen, Li, Sprooten, Emma, Strengman, Eric, Teumer, Alexander, Trabzuni, Daniah, Turner, Jessica, van Eijk, Kristel, van Erp, Theo G M, van Tol, Marie-Jose, Wittfeld, Katharina, Verhaaren, Benjamin F J, Wolf, Christiane, Woudstra, Saskia, Aleman, Andre, Alhusaini, Saud, Almasy, Laura, Binder, Elisabeth B, Brohawn, David G, Cantor, Rita M, Carless, Melanie A, Corvin, Aiden, DeStefano, Anita L, Czisch, Michael, Curran, Joanne E, Davies, Gail, de Almeida, Marcio A A, Delanty, Norman, Depondt, Chantal, Duggirala, Ravi, Dyer, Thomas D, Erk, Susanne, Fagerness, Jesen, Lambert, Jean-Charles, Fox, Peter T, Freimer, Nelson B, Gill, Michael, Göring, Harald H H, Hagler, Donald J, Hoehn, David, Holsboer, Florian, Hoogman, Martine, Hosten, Norbert, Jahanshad, Neda, Jack, Clifford R, Johnson, Matthew P, Kasperaviciute, Dalia, Kent, Jack W, Kochunov, Peter, Lancaster, Jack L, Lawrie, Stephen M, Liewald, David C, Mandl, René, Matarin, Mar, Mattheisen, Manuel, Struchalin, Maksim, Meisenzahl, Eva, Melle, Ingrid, Moses, Eric K, Mühleisen, Thomas W, Nauck, Matthias, Nöthen, Markus M, Olvera, Rene L, Pandolfo, Massimo, Pike, G Bruce, Puls, Ralf, Stankovich, Jim, Reinvang, Ivar, Rentería, Miguel E, Rietschel, Marcella, Roffman, Joshua L, Royle, Natalie A, Rujescu, Dan, Savitz, Jonathan, Schnack, Hugo G, Schnell, Knut, Seiferth, Nina, Smith, Albert Vernon, Ibrahim-Verbaas, Carla A, Smith, Colin, Steen, Vidar M, Valdés Hernández, Maria C, Van den Heuvel, Martijn, van der Wee, Nic J, Van Haren, Neeltje E M, Veltman, Joris A, Völzke, Henry, Walker, Robert, Westlye, Lars T, Fleischman, Debra, Whelan, Christopher D, Agartz, Ingrid, Boomsma, Dorret I, Cavalleri, Gianpiero L, Dale, Anders M, Djurovic, Srdjan, Drevets, Wayne C, Hagoort, Peter, Hall, Jeremy, Heinz, Andreas, Zijdenbos, Alex, Foroud, Tatiana M, Le Hellard, Stephanie, Macciardi, Fabio, Montgomery, Grant W, Poline, Jean Baptiste, Porteous, David J, Sisodiya, Sanjay M, Starr, John M, Sussmann, Jessika, den Heijer, Tom, Toga, Arthur W, Veltman, Dick J, Walter, Henrik, Weiner, Michael W, Andreassen, Ole A, Apostolova, Liana G, Bastin, Mark E, Blangero, John, Brunner, Han G, Buckner, Randy L, Mazoyer, Bernard, Cichon, Sven, Coppola, Giovanni, de Zubicaray, Greig I, Deary, Ian J, Donohoe, Gary, de Geus, Eco J C, Espeseth, Thomas, Fernández, Guillén, Glahn, David C, Grabe, Hans J, Coker, Laura H, Hardy, John, Hulshoff Pol, Hilleke E, Jenkinson, Mark, Kahn, René S, McDonald, Colm, McIntosh, Andrew M, McMahon, Francis J, McMahon, Katie L, Meyer-Lindenberg, Andreas, Morris, Derek W, Enzinger, Christian, Müller-Myhsok, Bertram, Nichols, Thomas E, Ophoff, Roel A, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W, Potkin, Steven G, Sämann, Philipp G, Saykin, Andrew J, Schumann, Gunter, Danoy, Patrick, Smoller, Jordan W, Wardlaw, Joanna M, Weale, Michael E, Martin, Nicholas G, Franke, Barbara, Wright, Margaret J, Thompson, Paul M, Amin, Najaf, Arfanakis, Konstantinos, van der Lijn, Fedde, van Buchem, Mark A, de Bruijn, Renée F A G, Beiser, Alexa, Dufouil, Carole, Huang, Juebin, Cavalieri, Margherita, Thomson, Russell, Niessen, Wiro J, Chibnik, Lori B, Gislason, Gauti K, Crivello, Fabrice, Hofman, Albert, Pikula, Aleksandra, Amouyel, Philippe, Freeman, Kevin B, Phan, Thanh G, Oostra, Ben A, Stein, Jason L, Medland, Sarah E, Vasquez, Alejandro Arias, Hibar, Derrek P, Fornage, Myriam, Consortium, Enhancing Neuro Imaging Genetics through Meta-Analysis, Nalls, Michael A, Uitterlinden, Andre G, Au, Rhoda, Elbaz, Alexis, Beare, Richard J, Debette, Stephanie, van Swieten, John C, Lopez, Oscar L, Harris, Tamara B, Chouraki, Vincent, Breteler, Monique M B, De Jager, Philip L, Becker, James T, Vernooij, Meike W, Knopman, David, Fazekas, Franz, Shulman, Joshua M, Wolf, Philip A, van der Lugt, Aad, Gudnason, Vilmundur, Longstreth, W. T., Brown, Matthew A, Bennett, David A, van Duijn, Cornelia M, Mosley, Thomas H, Schmidt, Reinhold, Tzourio, Christophe, Schmidt, Helena, Launer, Lenore J, Ikram, M Arfan, Seshadri, Sudha, Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology, Arias Vasquez, Alejandro, Senstad, Rudy E, Winkler, Anderson M, Srikanth, Velandai, Toro, Roberto, Appel, Katja, Bartecek, Richard, Bergmann, Ørjan, Bernard, Manon, Brown, Andrew A, Cannon, Dara M, Chakravarty, Mallar, Christoforou, Andrea, Domin, Martin, University of Washington [Seattle], University of California [Davis] (UC Davis), University of California, Center for Neuroscience, University of California-University of California, Icelandic Heart Association, Kopavogur, Iceland., Faculty of Medicine, University of Iceland [Reykjavik], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, The University of Texas Health Science Center at Houston (UTHealth), Human Genetics Center, Institut National de la Santé et de la Recherche Médicale (INSERM), U708, Neuroepidemiology, Paris, France, Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Institute of Molecular Biology and Biochemistry, Medical University Graz, Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Monash University [Melbourne], Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia, University of Tasmania [Hobart, Australia] (UTAS), Rush University Medical Center [Chicago], Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Université Lille Nord de France (COMUE), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department of Radiology, Mayo Clinic, Biospective [Montréal], Department of Neurology, Sint Franciscus Gasthuis, Rotterdam, The Netherlands, Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Department of Neurology, Medical University Graz, Graz, Austri, University of Queensland, Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia, Department of Biomedical Engineering, Illinois Institute of Technology (IIT), Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands, University of Mississippi Medical Center (UMMC), Delft University of Technology (TU Delft), Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Queensland Institute of Medical Research, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Department of Human Genetics [Nijmegen], Radboud University Medical Center [Nijmegen], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], National Institutes of Health [Bethesda] (NIH), Unité de recherche Neuroépidémiologie [CHU Pitié-Salpêtrière], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Murdoch Children's Research Institute (MCRI), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Harvard University [Cambridge], Harvard Medical School [Boston] (HMS), Mayo Clinic [Rochester], Human Genetics Group, University of Queensland Diamantina Institute, Princess Alexandra Hospital, Woolloongabba, Brisbane, Australia, Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands, University of Bordeaux, U708, Bordeaux, France, INSERM, Neuroepidemiology U708, Bordeaux, France, University of California (UC), University of California (UC)-University of California (UC), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), University of Queensland [Brisbane], Radboud University [Nijmegen], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Harvard University, Other departments, Human genetics, EMGO - Mental health, NCA - Attention & Cognition, Radiology & Nuclear Medicine, Epidemiology, Neurology, Cardiothoracic Surgery, Clinical Genetics, Internal Medicine, Biological Psychology, Neuroscience Campus Amsterdam - Attention & Cognition, and EMGO+ - Mental Health
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Netherlands Twin Register (NTR) ,genetics [Alzheimer Disease] ,Genome-wide association study ,DCN PAC - Perception action and control ,genetics [Cognition Disorders] ,Hippocampal formation ,Hippocampus ,0302 clinical medicine ,Polymorphism (computer science) ,Cognitive decline ,Genetics ,0303 health sciences ,Translational research Immune Regulation [ONCOL 3] ,Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3] ,genetics [Chromosomes, Human, Pair 12] ,genetics [Polymorphism, Single Nucleotide] ,Alzheimer's disease ,Genetic Markers ,medicine.medical_specialty ,DCN MP - Plasticity and memory ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3] ,03 medical and health sciences ,Meta-Analysis as Topic ,SDG 3 - Good Health and Well-being ,genetics [Dementia] ,Alzheimer Disease ,ddc:570 ,Internal medicine ,medicine ,Humans ,SNP ,Chromosome 12 ,030304 developmental biology ,Chromosomes, Human, Pair 12 ,[SCCO.NEUR]Cognitive science/Neuroscience ,medicine.disease ,Endocrinology ,Genetic Loci ,physiopathology [Hippocampus] ,Dementia ,Cognition Disorders ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Contains fulltext : 110608.pdf (Publisher’s version ) (Closed access) Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of
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42. Lifestyle transitions in plant pathogenic Colletotrichum fungi deciphered by genome and transcriptome analyses
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Jeffrey A. Rollins, Ken Shirasu, Jochen Kleemann, Emiel Ver Loren van Themaat, Narmada Shenoy, Hiroyuki Takahara, Christian Becker, Maria F. Torres, Zehua Chen, Noam Alkan, Martin B. Dickman, Michael Place, Pamela Gan, Christopher L. Schardl, Neil Moore, Michael R. Thon, Richard J. Howard, Christian Koch, Lucia Alvarado-Balderrama, Stefan G. Amyotte, Christopher Bauser, Robert H. Proctor, James A. Sweigard, Audrey D. Law, Bruce W. Birren, Jaeyoung Choi, Daniel G. Panaccione, Serenella A. Sukno, Itay Miyara, Lars M. Voll, Karl Nordström, Li-Jun Ma, Yasuyuki Kubo, Usha Rani Sikhakolli, Sarah Young, Mark A. Farman, Yong-Hwan Lee, Ester Alvarenga Santos Buiate, Ulla Neumann, Ulrike Damm, Mehdi Kabbage, H. Charlotte van der Does, Bernard Henrissat, Kurt Stüber, Dov Prusky, Marc-Henri Lebrun, Richard J. O'Connell, Shiguo Zhou, Richard Reinhardt, Stéphane Hacquard, Jonathan P. Duvick, Gabriel E. Rech, Frances Trail, Steve Rounsley, David C. Schwartz, Yoshitaka Takano, Paul Schulze-Lefert, Jo Anne Crouch, Ralph Panstruga, Barbara Kracher, David I. Heiman, Janine Altmüller, Jingze Zhang, Qiandong Zeng, Isa Will, Lynn Epstein, Lisa J. Vaillancourt, Department of Plant Microbe Interactions, Max Planck Institute for Plant Breeding Research (MPIPZ), Centro Hispano-Luso de Investigaciones Agrarias, Departamento de Microbiología y Genétic, Universidad de Salamanca, Department of Plant Pathology, University of Kentucky (UK), 1. Department of Plant Microbe Interactions, Fungal Biodiversity Centre, 3. Department of Plant Pathology, Kentucky State University, University of California (UC), 6. Department of Postharvest Science of Fresh Produce, Agricultural Research Organizati, Agricultural Research Organization, Cologne Center for Genomics, University of Cologne, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), GATC Biotech AG [Konstanz], Center for Genomics, Seoul National University [Seoul] (SNU), Systematic Mycology and Microbiology Laboratory, United States Department of Agriculture, DuPont Agricultural Biotechnology, Pioneer Hi-Bred International, Plant Immunity Research Group, RIKEN Plant Science Center, Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), 15. Department of Plant Pathology and Microbiology, Institute for Plant Genomics and Biotechnology, Borlaug Genomics and Bioinformatics Center, Texas, Texas A&M University System, Department of Biology, Division of Biochemistry, Friedrich-Alexander, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Laboratory of Plant Pathology, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University (KPU), BIOlogie et GEstion des Risques en agriculture (BIOGER), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, 6. Department of Postharvest Science of Fresh Produce, Agricultural Research Organization, Department of Computer Science, Central Microscopy, Department of Plant Developmental Biology, Division of Plant and Soil Sciences, West Virginia University, Institute for Biology I, Unit of Plant Molecular Cell Biology, Rheinisch-Westfälische Technische Hochschule, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Laboratory for Molecular and Computational Genomics, University of Wisconsin-Madison, Agriculture Research Service, National Center for Agricultural Utilization Research, 2. Centro Hispano-Luso de Investigaciones Agrarias, Departamento de Microbiología y Genética, Max Planck-Genome-centre Cologne (MP-GC), Max-Planck-Gesellschaft, University of Florida [Gainesville] (UF), Department of Plant Biology, Michigan State University [East Lansing], Michigan State University System-Michigan State University System, 12. Pioneer Hi-Bred International, Laboratory of Plant Pathology, Graduate School of Agriculture, Kyoto University, Department of Biology, Division of Biochemistry, Department of Plant Pathology and Microbiology, Institute for Plant Genomics and Biotechnology, University of Kentucky, University of California, Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Kyoto Prefectural University, AgroParisTech-Institut National de la Recherche Agronomique (INRA), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), University of Florida [Gainesville], Kyoto University [Kyoto], Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), and Vaillancourt, Lisa J
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operative targe ,[SDV]Life Sciences [q-bio] ,Arabidopsis ,specificity ,Models, Biological ,Transcriptome ,03 medical and health sciences ,host status ,Gene Expression Regulation, Fungal ,Genetics ,Colletotrichum ,Cluster Analysis ,Secondary metabolism ,Gene ,Colletotrichum higginsianum ,Phylogeny ,030304 developmental biology ,Plant Diseases ,Comparative genomics ,0303 health sciences ,biology ,030306 microbiology ,nonhost ,Gene Expression Profiling ,fungi ,Colletotrichum orbiculare ,Fungal genetics ,Gene Expression Regulation, Developmental ,food and beverages ,Sequence Analysis, DNA ,biology.organism_classification ,basal resistance ,Host-Pathogen Interactions ,Mitosporic Fungi ,Genome, Fungal ,effectors - Abstract
Colletotrichum species are fungal pathogens that devastate crop plants worldwide. Host infection involves the differentiation of specialized cell types that are associated with penetration, growth inside living host cells (biotrophy) and tissue destruction (necrotrophy). We report here genome and transcriptome analyses of Colletotrichum higginsianum infecting Arabidopsis thaliana and Colletotrichum graminicola infecting maize. Comparative genomics showed that both fungi have large sets of pathogenicity-related genes, but families of genes encoding secreted effectors, pectin-degrading enzymes, secondary metabolism enzymes, transporters and peptidases are expanded in C. higginsianum. Genome-wide expression profiling revealed that these genes are transcribed in successive waves that are linked to pathogenic transitions: effectors and secondary metabolism enzymes are induced before penetration and during biotrophy, whereas most hydrolases and transporters are upregulated later, at the switch to necrotrophy. Our findings show that preinvasion perception of plant-derived signals substantially reprograms fungal gene expression and indicate previously unknown functions for particular fungal cell types.
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43. A high density SNP array for the domestic horse and extant perissodactyla: utility for association mapping, genetic diversity, and phylogeny studies
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Matthew M. Binns, Tosso Leeb, Emmeline W. Hill, M. Cecilia T. Penedo, Claire M. Wade, Teruaki Tozaki, Gérard Guérin, June E Swinburne, Jessica Gurr, Kerstin Lindblad-Toh, Danika L. Bannasch, Telhisa Hasegawa, Mark Vaudin, Knut Røed, Stephanie J. Valberg, E. Bailey, Oliver A. Ryder, James R. Mickelson, Molly E. McCue, Jessica L. Petersen, Gabriella Lindgren, Ottmar Distl, McCue, Molly E., College of Veterinary Medicine, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Faculty of Veterinary Science, The University of Sydney, Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Equine Analysis Systems, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Equine Research Institute, Japan Racing Association, Animal Genomics Laboratory, School of Agriculture and Food Science, University College Dublin [Dublin] (UCD), Institute of Genetics, Vetsuisse Faculty, University of Bern, Department of Animal Bredding and Genetics, Swedish University of Agricultural Sciences (SLU), Veterinary Genetics Laboratory, Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, San Diego Zoo's Institute for Conservation Research, Animal Health Trust (AHT), Department of Molecular Genetics, Laboratory of Racing Chemistry, Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), University of Minnesota [Twin Cities], AgroParisTech-Institut National de la Recherche Agronomique (INRA), Department of Animal Breeding and Genetics, and Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge]
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Cancer Research ,Genotyping Techniques ,Genetic Linkage ,[SDV]Life Sciences [q-bio] ,Cell- och molekylärbiologi ,Population genetics ,Breeding ,Linkage Disequilibrium ,Gene Frequency ,Association mapping ,Genetics (clinical) ,Phylogeny ,Genetics ,0303 health sciences ,biology ,Chromosome Mapping ,Agriculture ,04 agricultural and veterinary sciences ,Genomics ,Biological Evolution ,SNP genotyping ,Medical Genetics ,SNP array ,Research Article ,Coat ,lcsh:QH426-470 ,Animal Types ,biology.animal_breed ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Animals ,Horses ,Molecular Biology ,Genotyping ,Biology ,Ecology, Evolution, Behavior and Systematics ,Perissodactyla ,030304 developmental biology ,Medicinsk genetik ,Population Biology ,0402 animal and dairy science ,Genetic Variation ,040201 dairy & animal science ,lcsh:Genetics ,Haplotypes ,Quarter horse ,Veterinary Science ,Cell and Molecular Biology - Abstract
An equine SNP genotyping array was developed and evaluated on a panel of samples representing 14 domestic horse breeds and 18 evolutionarily related species. More than 54,000 polymorphic SNPs provided an average inter-SNP spacing of ∼43 kb. The mean minor allele frequency across domestic horse breeds was 0.23, and the number of polymorphic SNPs within breeds ranged from 43,287 to 52,085. Genome-wide linkage disequilibrium (LD) in most breeds declined rapidly over the first 50–100 kb and reached background levels within 1–2 Mb. The extent of LD and the level of inbreeding were highest in the Thoroughbred and lowest in the Mongolian and Quarter Horse. Multidimensional scaling (MDS) analyses demonstrated the tight grouping of individuals within most breeds, close proximity of related breeds, and less tight grouping in admixed breeds. The close relationship between the Przewalski's Horse and the domestic horse was demonstrated by pair-wise genetic distance and MDS. Genotyping of other Perissodactyla (zebras, asses, tapirs, and rhinoceros) was variably successful, with call rates and the number of polymorphic loci varying across taxa. Parsimony analysis placed the modern horse as sister taxa to Equus przewalski. The utility of the SNP array in genome-wide association was confirmed by mapping the known recessive chestnut coat color locus (MC1R) and defining a conserved haplotype of ∼750 kb across all breeds. These results demonstrate the high quality of this SNP genotyping resource, its usefulness in diverse genome analyses of the horse, and potential use in related species., Author Summary We utilized the previously generated horse genome sequence and a large SNP database to design an ∼54,000 SNP assay for use in the domestic horse and related species. The utility of this SNP array was demonstrated through genome-wide linkage disequilibrium, inbreeding and genetic distance measurements within breeds, as well as multidimensional scaling and parsimony analysis. Association mapping confirmed a large conserved segment containing the chestnut coat color locus in domestic horses. We also assess the utility of the SNP array in related species, including the Przewalski's Horse, zebras, asses, tapirs, and rhinoceros. This SNP genotyping tool will facilitate many genetics applications in equids, including identification of genes for health and performance traits, and compelling studies of the origins of the domestic horse, diversity within breeds, and evolutionary relationships among related species.
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44. Assemblathon 1: A competitive assessment of de novo short read assembly methods
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Inanc Birol, Peter Skewes-Cox, Dariusz Przybylski, Paul J. Kersey, Guillaume Chapuis, Matthias Haimel, Sante Gnerre, Mark Diekhans, Petr Kosarev, Richard E. Green, Igor Seledtsov, Richard Durbin, Daniel S. Rokhsar, Miguel Betegon, Ngan Nguyen, Isaac Ho, J. Graham Ruby, Michelle Dimon, Aaron E. Darling, Ricardo H. Ramirez-Gonzalez, Daniel R. Zerbino, David R. Kelley, Ruibang Luo, Ian F Korf, Richard M. Leggett, Timothy I. Shaw, Keith Bradnam, Benedict Paten, Yingrui Li, Giles Hall, Vince Buffalo, Yinlong Xie, Shuangye Yin, Xiaoqiu Huang, Shaun D. Jackman, Victor V. Solovyev, Denis Vorobyev, Binghang Liu, T. Roderick Docking, Joseph L. DeRisi, Delphine Naquin, Ted Sharpe, Adam M. Phillippy, Mario Caccamo, Zemin Ning, Wing-Kin Sung, Jarrod Chapman, David B. Jaffe, John St. John, Pramila N. Ariyaratne, David Haussler, Fangfang Xia, Wen-Chi Chou, Sergey Koren, Dan MacLean, Joseph Fass, Rayan Chikhi, Iain MacCallum, Nicolas Maillet, Hung On Ken Yu, Nuno A. Fonseca, Dominique Lavenier, Michael C. Schatz, Dent Earl, Anuj Srivastava, Dawei Lin, Zhenyu Li, Wei Wu, Filipe J. Ribeiro, Shiaw-Pyng Yang, Jared T. Simpson, Center for Biomolecular Science and Engineering, University of California [Santa Cruz] (UC Santa Cruz), University of California (UC)-University of California (UC), Biomolecular Engineering Department, Genome Center [UC Davis], University of California [Davis] (UC Davis), Bioinformatics Core [University California Davis] (UC Davis), Computational and Mathematical Biology, Genome Institute of Singapore (GIS), School of computing [Singapore] (NUS), National University of Singapore (NUS), The Wellcome Trust Sanger Institute [Cambridge], European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Center for Research in Advanced Computing Systems (CRACS INESC), Faculdade de Ciências da Universidade do Porto (FCUP), Universidade do Porto = University of Porto-Universidade do Porto = University of Porto, Genome Sciences Centre [Vancouver] (GSC), British Columbia Cancer Agency, DOE Joint Genome Institute [Walnut Creek], Department of Molecular & Cell Biology [Berkeley], University of California [Berkeley] (UC Berkeley), Biological systems and models, bioinformatics and sequences (SYMBIOSE), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), Simons Center for Quantitative Biology [Cold Spring Harbor], Cold Spring Harbor Laboratory, Center for Bioinformatics and Computational Biology [Maryland] (CBCB), University of Maryland [College Park], University of Maryland System-University of Maryland System, National Biodefense Analysis and Countermeasures Center [Frederick], U.S. Social Security Administration, Monsanto Company, Institute of Bioinformatics [Georgia] (IOB), University of Georgia [USA], Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), Department of Biochemistry and Biophysics [San Francisco], University of California (UC), Biological and Medical Informatics [San Francisco] (BMI), University of California [San Francisco] (UC San Francisco), Department of Computer Science [Royal Holloway], Royal Holloway [University of London] (RHUL), Softberry Inc, Softberry, The Genome Analysis Centre (TGAC), Sainsbury Laboratory Cambridge University (SLCU), University of Cambridge [UK] (CAM), Computation Institute [Chicago], University of Chicago, Beijing Genomics Institute [Shenzhen] (BGI), Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Department of Computer Science [Ames], Iowa State University (ISU), University of California [Santa Cruz] (UCSC), University of California-University of California, Bioinformatics Core [UC Davis], Universidade do Porto-Universidade do Porto, University of California [Berkeley], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, University of California, University of California [San Francisco] (UCSF), and Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge]
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Genetics ,Resource ,0303 health sciences ,Genome ,Bioinformatics ,Sequence assembly ,Genomics ,Computational biology ,Sequence Analysis, DNA ,Biology ,Short read ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,03 medical and health sciences ,0302 clinical medicine ,Code (cryptography) ,Benchmark (computing) ,Data set (IBM mainframe) ,Base calling ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,030217 neurology & neurosurgery ,Genetics (clinical) ,030304 developmental biology - Abstract
Low-cost short read sequencing technology has revolutionized genomics, though it is only just becoming practical for the high-quality de novo assembly of a novel large genome. We describe the Assemblathon 1 competition, which aimed to comprehensively assess the state of the art in de novo assembly methods when applied to current sequencing technologies. In a collaborative effort, teams were asked to assemble a simulated Illumina HiSeq data set of an unknown, simulated diploid genome. A total of 41 assemblies from 17 different groups were received. Novel haplotype aware assessments of coverage, contiguity, structure, base calling, and copy number were made. We establish that within this benchmark: (1) It is possible to assemble the genome to a high level of coverage and accuracy, and that (2) large differences exist between the assemblies, suggesting room for further improvements in current methods. The simulated benchmark, including the correct answer, the assemblies, and the code that was used to evaluate the assemblies is now public and freely available from http://www.assemblathon.org/.
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- 2011
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45. On the Futility of Screening for Genes That Make You Fat
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Terho Lehtimäki, Emily Sonestedt, Göran Hallmans, Andy R Ness, Simin Liu, Tuija Tammelin, John J. Nolan, Massimo Mangino, Nicholas J. Timpson, George Dedoussis, Aline Meirhaeghe, Lu Qi, Pål R. Njølstad, Ruth J. F. Loos, Mustafa Atalay, Mao Fu, Natalia V. Rivera, Marju Orho-Melander, Thorkild I. A. Sørensen, Philippe Froguel, André G. Uitterlinden, Torben Hansen, Debbie A Lawlor, M. Carola Zillikens, Tapani Rönnemaa, Vilmundur Gudnason, Esther Zimmermann, Claes Ohlsson, Cornelia M. van Duijn, Paul M. Ridker, Marjo-Riitta Järvelin, Samia Mora, María Teresa Martínez Larrad, Alena Stančáková, Thomas Illig, Zoltán Kutalik, Sven Bergmann, Jonatan R. Ruiz, Luigi Palla, Kathleen A. Jablonski, Günther Silbernagel, Ulla Sovio, Soren Snitker, Karina Meidtner, Bo Isomaa, Stephen J. Sharp, Jana V. van Vliet-Ostaptchouk, Louis Pérusse, Mika Kähönen, Daniel I. Chasman, Najaf Amin, Johanna Kuusisto, Toshiko Tanaka, Ingrid B. Borecki, John-Olov Jansson, Christine Cavalcanti-Proença, N. Charlotte Onland-Moret, Kay-Tee Khaw, Camilla H. Sandholt, Ulf Ekelund, Luigi Ferrucci, Mark Walker, Yiqing Song, Jose C. Florez, Oluf Pedersen, Leif Groop, Ying Wu, Soren Brage, Tuomas O. Kilpeläinen, Anders Grøntved, Frida Renström, Meena Kumari, Stéphane Cauchi, Michael Boehnke, Tamara B. Harris, Christine S. Autenrieth, Jeffery Metter, Beverley Balkau, Dmitry Shungin, Karen L. Mohlke, Markku Laakso, Matti Uusitupa, Nicholas J. Wareham, Andreas Fritsche, Jaakko Tuomilehto, Albert Hofman, Shah Ebrahim, Mary F. Feitosa, Melissa E. Garcia, Stefan Johansson, Tim D. Spector, Paul W. Franks, E. Shyong Tai, Frank B. Hu, Jonathan T. Tan, Maarit Hakanen, Heiner Boeing, Manuel Serrano Ríos, Olli T. Raitakari, Michael Marmot, Meian He, Jennifer L. Bragg-Gresham, Claude Bouchard, Tariq Ahmad, Ellen W. Demerath, Keri L. Monda, Robert A. Scott, Marika Kaakinen, Chris Power, Stefania Bandinelli, Christina Holzapfel, Timo A. Lakka, Heather M. Stringham, Stavroula Kanoni, Elina Hyppönen, Pamela L. Lutsey, Internal Medicine, Medical Microbiology & Infectious Diseases, Epidemiology, Urology, Institute of Metabolic Science, MRC, Departments of Epidemiology and Nutrition, Harvard School of Public Health, Department of Clinical Sciences, Lund University Diabetes Centre-Lund University [Lund], Division of Epidemiology and Community Health, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Division of Cardiology, Duke University Medical Center, Brigham and Women's Hospital [Boston], Institute of Health Sciences and Biocenter Oulu, University of Oulu, Hagedorn Research Institute, Else Kroener Fresenius Centre - Zentralinstitut für Ernährungs und Lebensmittelfors (ZIEL), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Department of Population Health Sciences, University of Wisconsin-Madison, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Centre for Paediatric Epidemiology and Biostatistics, University College of London [London] (UCL), MRC Centre for Epidemiology of Child Health, UCL Institute of Child Health, Institut de biologie de Lille - UMS 3702 (IBL), Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Genetics, Université de Lausanne (UNIL), Department of Epidemiology and Public Health, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Department of Epidemiology, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association-Leibniz Association, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National University of Singapore (NUS)-Yong Loo Lin School of Medicine, King‘s College London, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, Division of Preventive Medicine, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Department of Internal Medicine, Erasmus University Medical Center [Rotterdam] (Erasmus MC), The Biostatistics Center, The George Washington University (GW), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Mental Health Sciences Unit, Department of Clinical Medicine, University of Bergen (UiB), Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Genetics, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Molecular Genetics Section, University of Groningen [Groningen]-University Medical Centre Groningen, Complex Genetics Section, University Medical Center [Utrecht], Julius Center for Health Sciences and Primary Care, Institute of Preventive Medicine, Copenhagen University Hospital, Department of Biomedical Sciences [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Genetic Epidemiology Unit, Medstar Research Institute, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Department of Nutrition-Dietetics, Harokopio University of Athens, Division of Statistical Genomics, Washington University School of Medicine, University of Maryland School of Medicine, University of Maryland System, Unit for Preventive Nutrition, Karolinska Institutet [Stockholm], Department of Physical Education and Sport, University of Granada [Granada], Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Hospital Clínico San Carlos, Department of Physiology, University of Eastern Finland-Institute of Biomedicine, The Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Institute of Sport Science and Clinical Biomechanics, University of Southern Denmark (SDU), Department of Public Health and Clinical Medicine/Nutritional Research, Umeå University, Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU)-Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Clinical Physiology, University of Tampere [Finland]-Tampere University Hospital, Steno Diabetes Centre, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health Sciences, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Odontology, Department of Medical Statistics, London School of Hygiene and Tropical Medicine (LSHTM), LIKES Research Center for Sport and Health Sciences, Finnish Institute of Occupational Health, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University (LSU)-Louisiana State University (LSU), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Division of Endocrinology, Diabetes and Nutrition, University of Maryland System-University of Maryland System, Institute of Cell and Molecular Biosciences, Newcastle University [Newcastle], Centre for Bone and Arthritis Research, Institute of Medicine-University of Gothenburg (GU), Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Centre for Medical Systems Biology, Faculty of Epidemiology and Population Health [London], Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland [Reykjavik], Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Department of Clinical Chemistry, Turku University Hospital (TYKS), Folkhälsan Research Centre, Department of Pediatrics, Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB), Center for Human Genetic Research and Diabetes Research Center, Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Program for Medical and Population Genetics, Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Center for Metabolic Disease Prevention, University of California [Los Angeles] (UCLA), University of California-University of California-David Geffen School of Medicine [Los Angeles], University of California-University of California, School of Oral and Dental Sciences, University of Bristol [Bristol], National University of Singapore (NUS), Department of Genomics of Common Disease, Imperial College London, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Department of Epidemiology and Biostatistics, Department of Life Course and Services, National Institute for Health and Welfare [Helsinki], Autard, Delphine, Lund University [Lund], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Universidad de Granada = University of Granada (UGR), University of Gothenburg (GU)-Institute of Medicine, University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), Medical Research Council (MRC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Brage, Soren [0000-0002-1265-7355], Sharp, Stephen [0000-0003-2375-1440], Sovio, Ulla [0000-0002-0799-1105], Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Hjelt Institute (-2014), Harvard University-Massachusetts Institute of Technology (MIT)-Harvard University-Massachusetts Institute of Technology (MIT), Kilpeläinen, Tuomas O, Qi, Lu, Brage, Soren, Sharp, Stephen J, Hypponen, Elina, and Loos, Ruth JF
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Male ,Heredity ,endocrine system diseases ,Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714 [VDP] ,Epidemiology ,Social and Behavioral Sciences ,no keywords ,MESH: Genotype ,0302 clinical medicine ,MESH: Child ,GENETIC-VARIANTS ,MESH: Proteins ,10. No inequality ,Child ,0303 health sciences ,Anthropometry ,MESH: Polymorphism, Single Nucleotide ,General Medicine ,11 Medical And Health Sciences ,Genomics ,MESH: Motor Activity ,Adipose Tissue ,Perspective ,Medicine ,Public Health ,WAIST CIRCUMFERENCE ,MESH: Adipose Tissue ,medicine.medical_specialty ,Genotype ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,Endocrinology and Diabetes ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Genomic Medicine ,Genetics ,Humans ,Genetic Testing ,Gene Prediction ,Biology ,Adipose Tissue/metabolism ,Adolescent ,Adult ,Aged ,Female ,Genetic Predisposition to Disease ,Motor Activity ,Obesity/genetics ,Obesity/metabolism ,Polymorphism, Single Nucleotide ,Proteins/genetics ,Risk Factors ,MESH: Adolescent ,Science & Technology ,MESH: Humans ,Computational Biology ,nutritional and metabolic diseases ,Proteins ,MESH: Adult ,Odds ratio ,medicine.disease ,Obesity ,RS9939609 POLYMORPHISM ,Endocrinology ,Anthropology ,Physiological Processes ,Body mass index ,MESH: Female ,Population Genetics ,obesity ,Genetic Screens ,Anatomy and Physiology ,FTO gene ,IDENTICAL-TWINS ,MESH: Risk Factors ,MESH: Obesity ,adolescents ,030212 general & internal medicine ,MESH: Aged ,MESH: Genetic Predisposition to Disease ,3142 Public health care science, environmental and occupational health ,ENVIRONMENT INTERACTION ,Genetic Epidemiology ,childhood obesity ,Life Sciences & Biomedicine ,Research Article ,Clinical Research Design ,UNITED-STATES ,WEIGHT-LOSS ,Childhood obesity ,body weight ,Medicine, General & Internal ,Genome Analysis Tools ,Internal medicine ,General & Internal Medicine ,medicine ,Allele ,Sports and Exercise Medicine ,Genetic Association Studies ,030304 developmental biology ,Nutrition ,Clinical Genetics ,Population Biology ,business.industry ,Human Genetics ,MESH: Male ,COMMON VARIANT ,meta-analysis ,Minor allele frequency ,BODY-MASS INDEX ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Genetics of Disease ,Genetic Polymorphism ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Meta-Analyses ,business ,Energy Metabolism ,genetic predisposition ,DIABETES PREVENTION - Abstract
Ruth Loos and colleagues report findings from a meta-analysis of multiple studies examining the extent to which physical activity attenuates effects of a specific gene variant, FTO, on obesity in adults and children. They report a fairly substantial attenuation by physical activity on the effects of this genetic variant on the risk of obesity in adults., Background The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). Methods and Findings All studies identified to have data on the FTO rs9939609 variant (or any proxy [r 2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A−) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20–1.26), but PA attenuated this effect (p interaction = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19–1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24–1.36). No such interaction was found in children and adolescents. Conclusions The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity. Please see later in the article for the Editors' Summary, Editors’ Summary Background Two in three Americans are overweight, of whom half are obese, and the trend towards increasing obesity is now seen across developed and developing countries. There has long been interest in understanding the impact of genes and environment when it comes to apportioning responsibility for obesity. Carrying a change in the FTO gene is common (found in three-quarters of Europeans and North Americans) and is associated with a 20%–30% increased risk of obesity. Some overweight or obese individuals may feel that the dice are loaded and there is little point in fighting the fat; it has been reported that those made aware of their genetic susceptibility to obesity may still choose a poor diet. A similar fatalism may occur when overweight and obese people consider physical activity. But disentangling the influence of physical activity on those genetically susceptible to obesity from other factors that might impact weight is not straightforward, as it requires large sample sizes, could be subject to publication bias, and may rely on less than ideal self-reporting methods. Why Was This Study Done? The public health ramifications of understanding the interaction between genetic susceptibility to obesity and physical activity are considerable. Tackling the rising prevalence of obesity will inevitably include interventions principally aimed at changing dietary intake and/or increasing physical activity, but the evidence for these with regards to those genetically susceptible has been lacking to date. The authors of this paper set out to explore the interaction between the commonest genetic susceptibility trait and physical activity using a rigorous meta-analysis of a large number of studies. What Did the Researchers Do and Find? The authors were concerned that a meta-analysis of published studies would be limited both by the data available to them and by possible bias. Instead of this more widely used approach, they took the literature search as their starting point, identified other studies through their collaborators’ network, and then undertook a meta-analysis of all available studies using a new and standardized analysis plan. This entailed an extremely large number of authors mining their data afresh to extract the relevant data points to enable such a meta-analysis. Physical activity was identified in the original studies in many different ways, including by self-report or by using an external measure of activity or heart rate. In order to perform the meta-analysis, participants were labeled as physically active or inactive in each study. For studies that had used a continuous scale, the authors decided that the bottom 20% of the participants were inactive (10% for children and adolescents). Using data from over 218,000 adults, the authors found that carrying a copy of the susceptibility gene increased the odds of obesity by 1.23-fold. But the size of this influence was 27% less in the genetically susceptible adults who were physically active (1.22-fold) compared to those who were physically inactive (1.30-fold). In a smaller study of about 19,000 children, no such effect of physical activity was seen. What Do these Findings Mean? This study demonstrates that people who carry the susceptibility gene for obesity can benefit from physical activity. This should inform health care professionals and the wider public that the view of genetically determined obesity not being amenable to exercise is incorrect and should be challenged. Dissemination, implementation, and ensuring uptake of effective physical activity programs remains a challenge and deserves further consideration. That the researchers treated “physically active” as a yes/no category, and how they categorized individuals, could be criticized, but this was done for pragmatic reasons, as a variety of means of assessing physical activity were used across the studies. It is unlikely that the findings would have changed if the authors had used a different method of defining physically active. Most of the studies included in the meta-analysis looked at one time point only; information about the influence of physical activity on weight changes over time in genetically susceptible individuals is only beginning to emerge. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001116. This study is further discussed in a PLoS Medicine Perspective by Lennert Veerman The US Centers for Disease Control and Prevention provides obesity-related statistics, details of prevention programs, and an overview on public health strategy in the United States A more worldwide view is given by the World Health Organization The UK National Health Service website gives information on physical activity guidelines for different age groups, while similar information can also be found from US sources
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- 2011
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46. Genome sequence, comparative analysis and population genetics of the domestic horse
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Elisa Magnani, Sarah Fryc, Teri L. Lear, James R. Mickelson, Evan Mauceli, Loren C. Skow, Tosso Leeb, Emmeline W. Hill, Ann-Christine Syvänen, Joy M. Raison, Snaevar Sigurdsson, S. Searle, J. Vogel, Leif Andersson, Robert C. Onofrio, Helmut Blöcker, Bhanu P. Chowdhary, Eric S. Lander, Teruaki Tozaki, Kerstin Lindblad-Toh, Ottmar Distl, Mariano Rocchi, Matthew M. Binns, Ted Sharpe, Claire M. Wade, Solomon G. Nergadze, Tara Biagi, Manuel Garber, T. Hasegawa, Sante Gnerre, Freyja Imsland, Anna Kiialainen, Maria Cecilia T. Penedo, Robert C. Edgar, M. F. Piras, Oliver A. Ryder, David L. Adelson, G. Della Valle, James N. MacLeod, Jerzy Jurka, Elena Giulotto, Gabriella Lindgren, June E Swinburne, K. H. Røed, James D. Murray, S. Pedroni, Terje Raudsepp, Jared White, S.J. Coleman, Monica Zoli, Michael C. Zody, Douglas F. Antczak, Jinze Liu, Mark Vaudin, Rebecca R. Bellone, Ernest Bailey, Gérard Guérin, Stephanie J. Valberg, Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Center for Human Genetic Research, Massachusetts General Hospital [Boston], Faculty of Veterinary Sciences, The University of Sydney, Dipartimento di Genetica e Microbiologia, Università di Pavia, Department of Medical Biochemistry and Microbiology, Uppsala University, Dipartimento di Biologia, Alma Mater Studiorum University of Bologna (UNIBO), Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, University of Adelaide, University of Tampa, Helmholtz Centre for Infection Research (HZI), Institute of Animal Breeding and Genetics, University of Veterinary Medecine Hannover, 45 Monterey Drive, Institute of Genetics, University of Bern, Veterinary Genetics Laboratory, University of California, The Wellcome Trust Sanger Institute [Cambridge], Cornell University, Royal Veterinary College, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Equine Research Institute, Japan Racing Association, Animal Genomics Laboratory, School of Agriculture, Food Science and Veterinary Medicine, University College Dublin [Dublin] (UCD), Genetic Information Research Institute, Department of Medical Sciences, Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences (SLU), Department of Computer Science, College of Veterinary Medecine, University of Minnesota [Twin Cities], University of Minnesota System-University of Minnesota System, Population Health and Reproduction, School of Veterinary Medicine, Department of Genetics and Microbiology, Università degli studi di Bari, San Diego Zoo's Institute for Conservation Research, College of Veterinary Medicine, Texas A&M University System, Animal Health Trust (AHT), Department of Molecular Genetics, Laboratory of Racing Chemistry, Department of Biology, Massachusetts Institute of Technology (MIT)-Howard Hugues Medical Institute, Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], Howard Hugues Medical Institute-Massachusetts Institute of Technology (MIT), Università degli Studi di Pavia, Cornell University [New York], Department of Animal Bredding and Genetics, University of Minnesota [Twin Cities] (UMN), Università degli studi di Bari Aldo Moro (UNIBA), and Howard Hughes Medical Institute (HHMI)-Massachusetts Institute of Technology (MIT)
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Genetics ,Whole genome sequencing ,0303 health sciences ,Multidisciplinary ,040301 veterinary sciences ,[SDV]Life Sciences [q-bio] ,Haplotype ,complete genome ,Chromosome ,04 agricultural and veterinary sciences ,sequencing ,Biology ,Genome ,horse ,0403 veterinary science ,03 medical and health sciences ,Horse genome ,Evolutionary biology ,Centromere ,evolution ,030304 developmental biology ,Segmental duplication ,Synteny - Abstract
A Horse Is a Horse, of Course The history of horse domestication is closely tied to the history of the human society. Wade et al. (p. 865 ) report on the sequencing and provide a single nucleotide polymorphism map of the horse ( Equus caballus ) genome. Horses are a member of the order perissodactyla (odd-toed animals with hooves). The analysis reveals an evolutionarily new centromere on equine chromosome 11 that displays properties of an immature but fully functioning centromere and is devoid of centromeric satellite sequence. The findings clarify the nature of genetic diversity within and across horse breeds and suggest that the horse was domesticated from a relatively large number of females, but few males.
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- 2009
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47. Exome Chip Analysis Identifies Low-Frequency and Rare Variants in MRPL38 for White Matter Hyperintensities on Brain Magnetic Resonance Imaging
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Jian, Xueqiu, Satizabal, Claudia L, Nyquist, Paul A, Mishra, Aniket, Adams, Hieab H H, Li, Shuo, Teumer, Alexander, Zhao, Wei, Freedman, Barry I, Saba, Yasaman, Yanek, Lisa R, Chauhan, Ganesh, Smith, Albert V, van Buchem, Mark A, Cushman, Mary, Royle, Natalie A, Bryan, R Nick, Niessen, Wiro J, Windham, Beverly G, DeStefano, Anita L, Habes, Mohamad, Heckbert, Susan R, Palmer, Nicholette D, Wittfeld, Katharina, Lewis, Cora E, Eiriksdottir, Gudny, Maillard, Pauline, Mathias, Rasika A, Homuth, Georg, Valdés-Hernández, Maria Del C, Divers, Jasmin, Beiser, Alexa S, Langner, Sönke, Rice, Kenneth M, Bis, Joshua C, Bastin, Mark E, Yang, Qiong, Maldjian, Joseph A, Starr, John M, Sidney, Stephen, Risacher, Shannon L, Uitterlinden, André G, Gudnason, Vilmundur G, Nauck, Matthias, Rotter, Jerome I, Smith, Jennifer A, Schreiner, Pamela J, Boerwinkle, Eric, van Duijn, Cornelia M, Mazoyer, Bernard, von Sarnowski, Bettina, Gottesman, Rebecca F, Levy, Daniel, Sigurdsson, Sigurdur, Vernooij, Meike W, Turner, Stephen T, Hsu, Fang-Chi, Schmidt, Reinhold, Wardlaw, Joanna M, Psaty, Bruce M, Mosley, Thomas H, DeCarli, Charles S, Saykin, Andrew J, Bowden, Donald W, Becker, Diane M, Deary, Ian J, Schmidt, Helena, Nho, Kwangsik, Kardia, Sharon L R, Ikram, M Arfan, Debette, Stéphanie, Grabe, Hans J, Longstreth, W. T., Seshadri, Sudha, Launer, Lenore J, Fornage, Myriam, Group, neuroCHARGE Working, Hofer, Edith, Hagenaars, Saskia P, Epidemiology, Medical Informatics, Radiology & Nuclear Medicine, Clinical Chemistry, Internal Medicine, Neurology, Plymouth University, Greifswald University Hospital, Indiana University School of Medicine, Indiana University System, Université Grenoble Alpes - UFR Sciences de l'Homme et de la Société (UGA UFR SHS), Université Grenoble Alpes (UGA), sans affiliation, Department of Neurology, Johns Hopkins University School of Medicine [Baltimore], Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Bruce E. Butler Laboratory, Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), China Agricultural University (CAU), General Internal Medicine, Johns Hopkins School of Medicine, INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, Department of Radiology [Leiden, The Netherlands], Leids Universitair Medisch Centrum [Leiden, The Netherlands], Image sciences institute - University of Utrecht (ISI), University Medical Center [Utrecht], Boston University [Boston] (BU), Perelman School of Medicine, University of Pennsylvania [Philadelphia], Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Neurology Department, Boston University School of Medicine (BUSM), Boston University [Boston] (BU)-Boston University [Boston] (BU), University of Washington [Seattle], University of Edinburgh, University of Miami [Coral Gables], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Faculty of Medicine, University of Iceland [Reykjavik], Institute of Clinical Chemistry and Laboratory Medicine, The University of Texas Health Science Center at Houston (UTHealth), Dept of Neurology, Univ Medicine of Greifswald, Germany, Paris-Jourdan Sciences Economiques (PSE), École normale supérieure - Paris (ENS Paris)-Institut National de la Recherche Agronomique (INRA)-École des hautes études en sciences sociales (EHESS)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS), Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Metacohorts Consortium, Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), University of California-University of California, Department of Physics [Stockholm], Stockholm University, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Recherche Agronomique (INRA)-École des hautes études en sciences sociales (EHESS)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS), and Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge]
- Subjects
0301 basic medicine ,Nonsynonymous substitution ,Aging ,Disease ,Cardiorespiratory Medicine and Haematology ,Cohort Studies ,0302 clinical medicine ,methods [Magnetic Resonance Imaging] ,genetics [Exome] ,2.1 Biological and endogenous factors ,magnetic resonance imaging ,Medicine ,Exome ,Aetiology ,ComputingMilieux_MISCELLANEOUS ,Genetics ,education.field_of_study ,cerebral small vessel disease ,Brain ,neuroCHARGE Working Group ,White Matter ,genetics [Genetic Variation] ,Stroke ,medicine.anatomical_structure ,Meta-analysis ,Neurological ,genetics [Mitochondrial Proteins] ,Cardiology and Cardiovascular Medicine ,white matter ,Clinical Sciences ,Population ,Article ,diagnostic imaging [White Matter] ,White matter ,Mitochondrial Proteins ,03 medical and health sciences ,Clinical Research ,Humans ,ddc:610 ,education ,Gene ,diagnostic imaging [Brain] ,Advanced and Specialized Nursing ,Neurology & Neurosurgery ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,Human Genome ,Neurosciences ,Genetic Variation ,Hyperintensity ,Brain Disorders ,meta-analysis ,030104 developmental biology ,Neurology (clinical) ,business ,exome ,030217 neurology & neurosurgery - Abstract
Background and Purpose— White matter hyperintensities (WMH) on brain magnetic resonance imaging are typical signs of cerebral small vessel disease and may indicate various preclinical, age-related neurological disorders, such as stroke. Though WMH are highly heritable, known common variants explain a small proportion of the WMH variance. The contribution of low-frequency/rare coding variants to WMH burden has not been explored. Methods— In the discovery sample we recruited 20 719 stroke/dementia-free adults from 13 population-based cohort studies within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, among which 17 790 were of European ancestry and 2929 of African ancestry. We genotyped these participants at ≈250 000 mostly exonic variants with Illumina HumanExome BeadChip arrays. We performed ethnicity-specific linear regression on rank-normalized WMH in each study separately, which were then combined in meta-analyses to test for association with single variants and genes aggregating the effects of putatively functional low-frequency/rare variants. We then sought replication of the top findings in 1192 adults (European ancestry) with whole exome/genome sequencing data from 2 independent studies. Results— At 17q25, we confirmed the association of multiple common variants in TRIM65 , FBF1 , and ACOX1 ( P −7 ). We also identified a novel association with 2 low-frequency nonsynonymous variants in MRPL38 (lead, rs34136221; P EA =4.5×10 −8 ) partially independent of known common signal ( P EA(conditional) =1.4×10 −3 ). We further identified a locus at 2q33 containing common variants in NBEAL1 , CARF , and WDR12 (lead, rs2351524; P all =1.9×10 −10 ). Although our novel findings were not replicated because of limited power and possible differences in study design, meta-analysis of the discovery and replication samples yielded stronger association for the 2 low-frequency MRPL38 variants ( P rs34136221 =2.8×10 −8 ). Conclusions— Both common and low-frequency/rare functional variants influence WMH. Larger replication and experimental follow-up are essential to confirm our findings and uncover the biological causal mechanisms of age-related WMH.
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48. AGTR1 variant rs2638355 is associated with increased salt sensitivity of blood pressure: a female-specific effect in individuals from the HyperPath cohort.
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Tchio C, Heydarpour M, Pojoga L, Taylor H, Williams G, Williams JS, and Seely EW
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- Humans, Female, Male, Middle Aged, Cohort Studies, Adult, Sex Factors, Genotype, Receptor, Angiotensin, Type 1 genetics, Blood Pressure genetics, Sodium Chloride, Dietary adverse effects, Hypertension genetics, Hypertension physiopathology, Polymorphism, Single Nucleotide
- Abstract
Objective: Salt-sensitive hypertension (SSH) affects approximately half of the hypertensive population, increasing the risk of vascular complications. The underlying pathophysiological mechanisms of SSH remain complex and need to be fully elucidated. Our prior research has identified genetic factors contributing to the salt sensitivity of blood pressure (SSBP), particularly involving genes regulating volume and blood pressure. We also observed enhanced peripheral vascular response to angiotensin II in humans with salt-sensitive hypertension. Given the pivotal role of the angiotensin II receptor type-1 (AT1R or AGTR1) in blood pressure and intravascular volume regulation, we hypothesized a genetic association between AGTR1 and SSBP., Methods: Our study involved 240 individuals of European ancestry from the HyperPATH cohort, examined under restricted and high dietary salt conditions. We employed a tagging single nucleotide variant approach to genotype participants at AGTR1 ., Results: Our regression model revealed a significant association between the rs2638355 (A/G) variant and salt-sensitive systolic blood pressure (SS-SBP), and rs2638355 increased AGTR1 gene expression. Notably, carriers of the risk-allele of the noncoding regulatory variant rs2638355 exhibited higher systolic blood pressure under high salt diet conditions than nonrisk allele individuals. A sex-stratified analysis showed this salt-driven effect on systolic blood pressure was significant only in females, underscoring the role of dietary salt in modulating genetic effects in this group. Furthermore, a restricted salt diet in these individuals diminished blood pressure and negated the blood pressure phenotype-genotype association., Conclusion: Overall, our findings could aid in pinpointing individuals with salt-sensitive blood pressure among hypertensive patients, especially considering dietary and sex-specific factors., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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49. MalKinID: A Classification Model for Identifying Malaria Parasite Genealogical Relationships Using Identity-by-Descent.
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Wong W, Wang L, Schaffner SS, Li X, Cheeseman I, Anderson TJC, Vaughan A, Ferdig M, Volkman SK, Hartl DL, and Wirth DF
- Abstract
Pathogen genomics is a powerful tool for tracking infectious disease transmission. In malaria, identity-by-descent (IBD) is used to assess the genetic relatedness between parasites and has been used to study transmission and importation. In theory, IBD can be used to distinguish genealogical relationships to reconstruct transmission history or identify parasites for quantitative-trait-locus experiments. MalKinID (Malaria Kinship Identifier) is a new classification model designed to identify genealogical relationships among malaria parasites based on genome-wide IBD proportions and IBD segment distributions. MalKinID was calibrated to the genomic data from three laboratory-based genetic crosses (yielding 440 parent-child [PC] and 9060 full-sibling [FS] comparisons). MalKinID identified lab generated F1 progeny with >80% sensitivity and showed that 0.39 (95% CI 0.28, 0.49) of the second-generation progeny of a NF54 and NHP4026 cross were F1s and 0.56 (0.45, 0.67) were backcrosses of an F1 with the parental NF54 strain. In simulated outcrossed importations, MalKinID reconstructs genealogy history with high precision and sensitivity, with F1-scores exceeding 0.84. However, when importation involves inbreeding, such as during serial co-transmission, the precision and sensitivity of MalKinID declined, with F1-scores (the harmonic mean of precision and sensitivity) of 0.76 (0.56, 0.92) and 0.23 (0.0, 0.4) for PC and FS and <0.05 for second-degree and third-degree relatives. Disentangling inbred relationships required adapting MalKinID to perform multi-sample comparisons. Genealogical inference is most powered when 1) outcrossing is the norm or 2) multi-sample comparisons based on a predefined pedigree are used. MalKinID lays the foundations for using IBD to track parasite transmission history and for separating progeny for quantitative-trait-locus experiments., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)
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- 2024
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50. ZBTB7A is a modulator of KDM5-driven transcriptional networks in basal breast cancer.
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DiCiaccio B, Seehawer M, Li Z, Patmanidis A, Bui T, Foidart P, Nishida J, D'Santos CS, Papachristou EK, Papanastasiou M, Reiter AH, Qiu X, Li R, Jiang Y, Huang XY, Simeonov A, Kales SC, Rai G, Lal-Nag M, Jadhav A, Brown M, Carroll JS, Long HW, and Polyak K
- Abstract
We previously described that the KDM5B histone H3 lysine 4 demethylase is an oncogene in estrogen-receptor-positive breast cancer. Here, we report that KDM5A is amplified and overexpressed in basal breast tumors, and KDM5 inhibition (KDM5i) suppresses the growth of KDM5-amplified breast cancer cell lines. Using CRISPR knockout screens in a basal breast cancer cell line with or without KDM5i, we found that deletion of the ZBTB7A transcription factor and core SAGA complex sensitizes cells to KDM5i, whereas deletion of RHO-GTPases leads to resistance. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed co-localization of ZBTB7A and KDM5A/B at promoters with high histone H3K4me3 and dependence of KDM5A chromatin binding on ZBTB7A. ZBTB7A knockout altered the transcriptional response to KDM5i at NF-κB targets and mitochondrion-related pathways. High expression of ZBTB7A in triple-negative breast cancer is significantly associated with poor response to neoadjuvant chemotherapy. Our work furthers the understanding of KDM5-mediated gene regulation and identifies mediators of sensitivity to KDM5i., Competing Interests: Declaration of interests K.P. serves on the scientific advisory boards of Ideaya Biosciences and Scorpion Therapeutics, holds equity options in Scorpion Therapeutics and Ideaya Biosciences, and receives sponsored research funding from Novartis, where she also consults. H.W.L. receives research funding from Novartis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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