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1,756 results on '"National Institute of Health, Bethesda"'

1. Two-locus genome-wide linkage scan for prostate cancer susceptibility genes with an interaction effect

Author: Department of Internal Medicine and Urology, University of Michigan, Ann Arbor, MI, USA, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA, Department of Genetics, University of North Carolina, Chapel Hill, NC, USA, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA, Department of Genetics, University of North Carolina, Chapel Hill, NC, USA, ; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA, Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA, National Human Genome Research Institute, National Institute of Health, Bethesda, MD, USA, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA, ; Translational Genomics Research Institute (TGen), Phoenix, AZ, USA, ; Medical Center Blvd, Winston-Salem, NC, 27157, USA, ; Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Urology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Radiation Sciences, Oncology, University of Ume??, Ume??, Sweden, Department of Urology, University of Tampere and Tampere University Hospital, Tampere, Finland, ; Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland, Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA, USA, Ann Arbor, Isaacs, William B., Cooney, Kathleen A., Wiley, Kathleen E., Trent, Jeffrey M., Dimitrov, Latchezar, Chang, Bao-Li, Lange, Ethan M., Suh, Edward, Gillanders, Elizabeth M., Lange, Leslie A., Xu, Jianfeng, Valis, Christopher J., Baffoe-Bonnie, Agnes, Zheng, S. Lilly, Fredriksson, Henna, Matikainen, Mika P., Gronberg, Henrik, Tammela, Teuvo, Bailey-Wilson, Joan E., Walsh, Patrick C., Schleutker, Johanna, Ikonen, Tarja, Langefeld, Carl D., Isaacs, Sarah D., Wiklund, Fredrik, Department of Internal Medicine and Urology, University of Michigan, Ann Arbor, MI, USA, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA, Department of Genetics, University of North Carolina, Chapel Hill, NC, USA, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA, Department of Genetics, University of North Carolina, Chapel Hill, NC, USA, ; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA, Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA, National Human Genome Research Institute, National Institute of Health, Bethesda, MD, USA, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA, ; Translational Genomics Research Institute (TGen), Phoenix, AZ, USA, ; Medical Center Blvd, Winston-Salem, NC, 27157, USA, ; Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Urology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Radiation Sciences, Oncology, University of Ume??, Ume??, Sweden, Department of Urology, University of Tampere and Tampere University Hospital, Tampere, Finland, ; Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland, Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA, USA, Ann Arbor, Isaacs, William B., Cooney, Kathleen A., Wiley, Kathleen E., Trent, Jeffrey M., Dimitrov, Latchezar, Chang, Bao-Li, Lange, Ethan M., Suh, Edward, Gillanders, Elizabeth M., Lange, Leslie A., Xu, Jianfeng, Valis, Christopher J., Baffoe-Bonnie, Agnes, Zheng, S. Lilly, Fredriksson, Henna, Matikainen, Mika P., Gronberg, Henrik, Tammela, Teuvo, Bailey-Wilson, Joan E., Walsh, Patrick C., Schleutker, Johanna, Ikonen, Tarja, Langefeld, Carl D., Isaacs, Sarah D., and Wiklund, Fredrik
Abstract: Prostate cancer represents a significant worldwide public health burden. Epidemiological and genetic epidemiological studies have consistently provided data supporting the existence of inherited prostate cancer susceptibility genes. Segregation analyses of prostate cancer suggest that a multigene model may best explain familial clustering of this disease. Therefore, modeling gene???gene interactions in linkage analysis may improve the power to detect chromosomal regions harboring these disease susceptibility genes. In this study, we systematically screened for prostate cancer linkage by modeling two-locus gene???gene interactions for all possible pairs of loci across the genome in 426 prostate cancer families from Johns Hopkins Hospital, University of Michigan, University of Ume??, and University of Tampere. We found suggestive evidence for an epistatic interaction for six sets of loci (target chromosome-wide/reference marker-specific P???0.0001). Evidence for these interactions was found in two independent subsets from within the 426 families. While the validity of these results requires confirmation from independent studies and the identification of the specific genes underlying this linkage evidence, our approach of systematically assessing gene???gene interactions across the entire genome represents a promising alternative approach for gene identification for prostate cancer.
Published: 2006

2. Comparing nonrigid registration techniques for motion corrected MR prostate diffusion imaging

Author: Choyke, P. [Molecular Imaging Program, NCI, National Institute of Health, Bethesda, Maryland 20892 (United States)]
Published: 2015
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3. Structure, dynamics and biophysics of the cytoplasmic protein–protein complexes of the bacterial phosphoenolpyruvate: Sugar phosphotransferase system

Author: Venditti, Vincenzo [National Institute of Health, Bethesda, MD (United States)]
Published: 2013
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4. Determination of gene dosage by a quantitative adaptation of the polymerase chain reaction (gd-PCR): Rapid detection of deletions and duplications of gene sequences

Author: Wertheimer, E [National Institute of Health, Bethesda, MD (United States)]
Published: 1994
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5. Fluctuations of the probability density of diffusing particles for different realizations of a random medium

Author: Weiss, G [Department of Physics, Bar-Ilan University, Ramat-Gan 52900 (Israel) National Institute of Health, Bethesda, Maryland 20892 (United States)]
Published: 1994
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6. Genomic organization and chromosomal localization of the T-cell antigen 4-1BB

Author: Kozak, C [National Institute of Health, Bethesda, MD (United States)]
Published: 1994

7. Progression of uremic hyperparathyroidism involves allelic loss on chromosome 11

Author: Marx, S [National Institute of Health, Bethesda, MD (United States)]
Published: 1993
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8. Organization of the human T cell receptor [zeta]/[eta] gene and its genetic linkage to the Fc[gamma]RII-Fc[gamma]RIII gene cluster

Author: Weissman, A [DCBDC/NCI NIH, Bethesda, MD (United States) DCBDC/National Cancer Institute National Institute of Health, Bethesda, MD (United States)]
Published: 1992

9. Novel genetic loci associated with hippocampal volume

Author: 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
Subjects: 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
Published: 2017
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10. Novel genetic loci underlying human intracranial volume identified through genome-wide association

Author: 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
Subjects: 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.
Published: 2016
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11. Common genetic variants influence human subcortical brain structures

Author: Hibar, Derrek P, Stein, Jason L, Aribisala, Benjamin S, de Zubicaray, Greig I, Dillman, Allissa, Duggirala, Ravi, Dyer, Thomas D, Erk, Susanne, Fedko, Iryna O, Ferrucci, Luigi, Foroud, Tatiana M, Fox, Peter T, Fukunaga, Masaki, Armstrong, Nicola J, Gibbs, J Raphael, Göring, Harald H H, Green, Robert C, Guelfi, Sebastian, Hansell, Narelle K, Hartman, Catharina A, Hegenscheid, Katrin, Heinz, Andreas, Hernandez, Dena G, Heslenfeld, Dirk J, Bernard, Manon, Hoekstra, Pieter J, Holsboer, Florian, Homuth, Georg, Hottenga, Jouke-Jan, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Kanai, Ryota, Keil, Maria, Bohlken, Marc M, Kent, Jack W, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Liu, Xinmin, Longo, Dan L, McMahon, Katie L, Meisenzahl, Eva, Melle, Ingrid, Mohnke, Sebastian, Boks, Marco P, Montgomery, Grant W, Mostert, Jeanette C, Mühleisen, Thomas W, Nalls, Michael A, Nichols, Thomas E, Nilsson, Lars G, Nöthen, Markus M, Ohi, Kazutaka, Olvera, Rene L, Perez-Iglesias, Rocio, Bralten, Janita, Pike, G Bruce, Potkin, Steven G, Reinvang, Ivar, Reppermund, Simone, Rietschel, Marcella, Romanczuk-Seiferth, Nina, Rosen, Glenn D, Rujescu, Dan, Schnell, Knut, Schofield, Peter R, Brown, Andrew A, Smith, Colin, Steen, Vidar M, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Turner, Jessica A, Valdés Hernández, Maria C, van 't Ent, Dennis, Chakravarty, M Mallar, van der Brug, Marcel, van der Wee, Nic J A, van Tol, Marie-Jose, Veltman, Dick J, Wassink, Thomas H, Westman, Eric, Zielke, Ronald H, Zonderman, Alan B, Ashbrook, David G, Hager, Reinmar, Chen, Qiang, Lu, Lu, McMahon, Francis J, Morris, Derek W, Williams, Robert W, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Cahn, Wiepke, Calhoun, Vince D, Cavalleri, Gianpiero L, Ching, Christopher R K, Crespo-Facorro, Benedicto, Dale, Anders M, Davies, Gareth E, Delanty, Norman, Depondt, Chantal, Djurovic, Srdjan, Drevets, Wayne C, Espeseth, Thomas, Gollub, Randy L, Ho, Beng-Choon, Renteria, Miguel E, Cuellar-Partida, Gabriel, Hoffmann, Wolfgang, Hosten, Norbert, Kahn, René S, Le Hellard, Stephanie, Meyer-Lindenberg, Andreas, Müller-Myhsok, Bertram, Nauck, Matthias, Nyberg, Lars, Pandolfo, Massimo, Penninx, Brenda W J H, den Braber, Anouk, Roffman, Joshua L, Sisodiya, Sanjay M, Smoller, Jordan W, van Bokhoven, Hans, van Haren, Neeltje E M, Völzke, Henry, Walter, Henrik, Weiner, Michael W, Wen, Wei, White, Tonya, Giddaluru, Sudheer, Agartz, Ingrid, Andreassen, Ole A, Blangero, John, Boomsma, Dorret I, Brouwer, Rachel M, Cannon, Dara M, Cookson, Mark R, de Geus, Eco J C, Deary, Ian J, Donohoe, Gary, Goldman, Aaron L, Fernández, Guillén, Fisher, Simon E, Francks, Clyde, Glahn, David C, Grabe, Hans J, Gruber, Oliver, Hardy, John, Hashimoto, Ryota, Hulshoff Pol, Hilleke E, Jönsson, Erik G, Grimm, Oliver, Kloszewska, Iwona, Lovestone, Simon, Mattay, Venkata S, Mecocci, Patrizia, McDonald, Colm, McIntosh, Andrew M, Ophoff, Roel A, Paus, Tomas, Pausova, Zdenka, Ryten, Mina, Guadalupe, Tulio, Sachdev, Perminder S, Saykin, Andrew J, Simmons, Andy, Singleton, Andrew, Soininen, Hilkka, Wardlaw, Joanna M, Weale, Michael E, Weinberger, Daniel R, Adams, Hieab H H, Launer, Lenore J, Hass, Johanna, Seiler, Stephan, Schmidt, Reinhold, Chauhan, Ganesh, Satizabal, Claudia L, Becker, James T, Yanek, Lisa, van der Lee, Sven J, Ebling, Maritza, Fischl, Bruce, Longstreth, W. T., Woldehawariat, Girma, Greve, Douglas, Schmidt, Helena, Nyquist, Paul, Vinke, Louis N, van Duijn, Cornelia M, Xue, Luting, Mazoyer, Bernard, Bis, Joshua C, Gudnason, Vilmundur, Seshadri, Sudha, Holmes, Avram J, Ikram, M Arfan, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, EPIGEN, IMAGEN, SYS, Martin, Nicholas G, Wright, Margaret J, Schumann, Gunter, Franke, Barbara, Hoogman, Martine, Thompson, Paul M, Medland, Sarah E, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jagust, William, Trojanowki, John Q, Beckett, Laurel, Arias-Vasquez, Alejandro, Janowitz, Deborah, Morris, John, Shaw, Leslie M, Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Jia, Tianye, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, Davie, Mesulman, M Marcel, Potter, William, Snyder, Peter, Schwartz, Adam, Montine, Tom, Kim, Sungeun, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Harvey, Danielle, Klein, Marieke, Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCarli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Kraemer, Bernd, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Lee, Phil H, Landau, Susan, Cairns, Nigel J, Householder, Erin, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Figurski, Michal, Olde Loohuis, Loes M, Crawford, Karen, Neu, Scott, Potkin, Steven, Shen, Li, Faber, Kelley, Nho, Kwangsik, Luciano, Michelle, Thal, Leon, Frank, Richard, Snyder, Peter J, Buckholtz, Neil, Macare, Christine, Albert, Marilyn, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Carter, Raina, Dolen, Sara, Gutman, Boris A, Schneider, Lon S, Mather, Karen A, Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L, Lord, Joanne L, Desrivières, Sylvane, Mattheisen, Manuel, Mason, Sara S, Albers, Colleen S, Knopman, David, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Milaneschi, Yuri, Honig, Lawrence S, Bell, Karen L, Ances, Beau, Morris, John C, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Oliver, Angela, Marson, Daniel, Griffith, Randall, Clark, David, Geldmacher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, deToledo-Morrell, Leyla, Shah, Raj C, Papmeyer, Martina, Duara, Ranjan, Varon, Daniel, Greig, Maria T, Roberts, Peggy, Onyike, Chiadi, D'Agostino, Daniel, Kielb, Stephanie, Galvin, James E, Pogorelec, Dana M, Ramasamy, Adaikalavan, Cerbone, Brittany, Michel, Christina A, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, De Santi, Susan, Doraiswamy, P Murali, Petrella, Jeffrey R, Wong, Terence Z, Arnold, Steven E, Risacher, Shannon L, Karlawish, Jason H, Wolk, David, Smith, Charles D, Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L, Oakley, MaryAnn, Roiz-Santiañez, Roberto, Simpson, Donna M, Porsteinsson, Anton P, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Ismail, M Saleem, Brand, Connie, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Rose, Emma J, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Lah, James J, Salami, Alireza, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H S, Lu, Po H, Bartzokis, George, Sämann, Philipp G, Graff-Radford, Neill R, Parfitt, Francine, Kendall, Tracy, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H, Jahanshad, Neda, Schmaal, Lianne, Carson, Richard E, MacAvoy, Martha G, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Yuek Robin, Feldman, Howard, Schork, Andrew J, Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristine, Shin, Jean, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Strike, Lachlan T, Marshall, Gad, Frey, Meghan, Yesavage, Jerome, Taylor, Joy L, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N, Belden, Christine M, Jacobson, Sandra A, Teumer, Alexander, Sirrel, Sherye A, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Allard, Joanne, Lerner, Alan, van Donkelaar, Marjolein M J, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichael, Owen, Olichney, John, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, van Eijk, Kristel R, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Walters, Raymond K, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W, Kataki, Maria, Adeli, Anahita, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Westlye, Lars T, Anderson, Karen, Santulli, Robert B, Kitzmiller, Tamar J, Schwartz, Eben S, Sink, Kaycee M, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Whelan, Christopher D, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Finger, Elizabether, Toro, Roberto, Winkler, Anderson M, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K, Ponto, Laura L Boles, Zwiers, Marcel P, Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Amin, Najaf, Becker, Diane, Alhusaini, Saud, Beiser, Alexa, Debette, Stéphanie, DeStefano, Anita, Hofer, Edith, Hofman, Albert, Niessen, Wiro J, Smith, Albert, Tzourio, Christophe, Vaidya, Dhananjay, Athanasiu, Lavinia, Vernooij, Meike W, Goldstein, David B, Heinzen, Erin L, Shianna, Kevin, Radtke, Rodney, Ottmann, Ruth, Albrecht, Lisa, Andrew, Chris, Arroyo, Mercedes, Artiges, Eric, Ehrlich, Stefan, Aydin, Semiha, Bach, Christine, Banaschewski, Tobias, Barbot, Alexis, Barker, Gareth, Boddaert, Nathalie, Bokde, Arun, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Hakobjan, Marina M H, Büchel, Christian, Cachia, Arnaud, Cattrell, Anna, Conrod, Patricia, Constant, Patrick, Crombag, Hans, Czech, Katharina, Dalley, Jeffrey, Decideur, Benjamin, Desrivieres, Sylvane, Hartberg, Cecilie B, Fadai, Tahmine, Flor, Herta, Frouin, Vincent, Fuchs, Birgit, Gallinat, Jürgen, Garavan, Hugh, Briand, Fanny Gollier, Gowland, Penny, Head, Kay, Heinrichs, Bert, Haukvik, Unn K, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ittermann, Bernd, Ivanov, Nikolay, Jones, Jennifer, Klaassen, Arno, Heister, Angelien J G A M, Lalanne, Christophe, Lathrop, Mark, Lanzerath, Dirk, Lemaitre, Hervé, Lüdemann, Katharina, Mallik, Catherine, Mangin, Jean-François, Mann, Karl, Mar, Adam, Hoehn, David, Martinot, Jean-Luc, Massicotte, Jessica, Mennigen, Eva, Mesquita de Carvahlo, Fabiana, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nees, Frauke, Nymberg, Charlotte, Paillere, Marie-Laure, Wittfeld, Katharina, Kasperaviciute, Dalia, Pena-Oliver, Yolanda, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Reed, Laurence, Robert, Gabriel, Reuter, Jan, Liewald, David C M, Ripke, Stephan, Ripley, Tamzin, Robbins, Trevor, Rodehacke, Sarah, Romanowski, Alexander, Ruggeri, Barbara, Schilling, Christina, Schmäl, Christine, Schmidt, Dirk, Lopez, Lorna M, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Schwartz, Yannick, Smolka, Michael, Sommer, Wolfgang, Spanagel, Rainer, Speiser, Claudia, Spranger, Tade, Stedman, Alicia, Makkinje, Remco R R, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Ströhle, Andreas, Struve, Maren, Subramaniam, Naresh, Theobald, David, Topper, Lauren, Vollstaedt-Klein, Sabine, Walaszek, Bernadeta, Matarin, Mar, Weiß, Katharina, Werts, Helen, Whelan, Robert, Williams, Steve, Yacubian, Juliana, Ziesch, Veronika, Zilbovicius, Monica, Wong, C Peng, Lubbe, Steven, Naber, Marlies A M, Martinez-Medina, Lourdes, Kepa, Agnes, Fernandes, Alinda, Tahmasebi, Amir, Abrahamowicz, Michal, Gaudet, Daniel, Leonard, Gabriel, Perron, Michel, Richer, Louis, Seguin, Jean, McKay, D Reese, Veillette, Suzanne, Needham, Margaret, Nugent, Allison C, Pütz, Benno, Abramovic, Lucija, Royle, Natalie A, Sprooten, Emma, Trabzuni, Daniah, van der Marel, Saskia S L, van Hulzen, Kimm J E, Walton, Esther, Wolf, Christiane, Almasy, Laura, Ames, David, Andersson, Micael, Arepalli, Sampath, Assareh, Amelia A, Bastin, Mark E, Brodaty, Henry, Bulayeva, Kazima B, Carless, Melanie A, Cichon, Sven, Corvin, Aiden, Curran, Joanne E, Czisch, Michael, MUMC+: DA Klinische Genetica (5), RS: GROW - Developmental Biology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Université de Montréal. Faculté de médecine. Département de psychiatrie et d'addictologie, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), QIMR Berghofer Medical Research Institute, Department of Psychiatry, Donders Centre for Neuroscience, Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, PRES Sorbonne Paris Cité, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, University Medical Center [Utrecht], European Commission, University of Edinburgh, Lagos State University (LASU), Heriot-Watt University [Edinburgh] (HWU), Unité d'expérimentation sur les Ruminants de Theix, Institut National de la Recherche Agronomique (INRA), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], University of Oslo (UiO), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], School of Technical Physics, Xidian University, Dept. of Mechanical Engineering, McMaster University [Hamilton, Ontario], Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Haukeland University Hospital, University of Bergen (UiB), Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 (PC2A), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Universität Heidelberg [Heidelberg] = Heidelberg University, 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 ), Georgia Institute of Technology [Atlanta], National Institutes of Health [Bethesda] (NIH), Yale University [New Haven], Massachusetts General Hospital [Boston], Mental Health Sciences Unit, University College of London [London] (UCL), Beijing Normal University (BNU), Indiana University School of Medicine, Indiana University System, Indiana Alzheimer Disease Center, Indiana University System-Indiana University System, Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, University of California (UC), Medstar Research Institute, 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, Universität Bonn = University of Bonn, Institute of Human Genetics, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], VU University Medical Center [Amsterdam], 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), 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), Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå 901 87, Sweden, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), 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), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), The Hospital for sick children [Toronto] (SickKids), 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, Department of Genomics of Common Disease, Imperial College London, Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Deutsche Bundesbank, Department of Neurology and Neurosurgery [Montreal], McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), MetaGenoPolis, Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway, UCL Institute of Neurology and Epilepsy Society, Department of Medicine, Clinical And Experimental Epilepsy, Dpt of Psychiatry [New Haven], Yale School of Medicine [New Haven, Connecticut] (YSM), Hartford Hospital, Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Statistical Genetics Group, State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Department of Genetics, King Faisal Specialist Hospital and Research Centre (KFSH & RC), Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Dundee Technopole, CXR Biosciences Ltd, Ninewells Hospital and Medical School, Biomedical Research Centre, University of Dundee, 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, Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Dementia Collaborative Research Centre, N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Texas Biomedical Research Institute [San Antonio, TX], Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Division of Medical Genetics, University of Basel (Unibas), Trinity College Dublin-St. James's Hospital, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Department of Materials Science & Metallurgy, University of Cambridge [UK] (CAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], School of Psychology, University of Queensland, Laboratory of Neurogenetics, The University of Texas Health Science Center at Houston (UTHealth), Department of Genomics, Department of Medical and Molecular Genetics, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan, Public Health Genomics Unit, Department of Biomolecular Engineering, Rheinische Friedrich-Wilhelms-Universität Bonn, Estación Experimental de Pastos y Forrajes 'Indio Hatuey', University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Department of Psychiatry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan, Department of Radiology, Mayo Clinic, Department of Clinical Neurology [Oxford], University of Oxford-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], University of Maryland School of Medicine, University of Maryland System, University of Sussex, Institute of Cognitive Neuroscience, United Kingdom Met Office [Exeter], University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Department of Civil and Structural Engineering, The Hong Kong Polytechnic University [Hong Kong] (POLYU)-The Hong Kong Polytechnic University [Hong Kong] (POLYU), Columbia University Irving Medical Center (CUIMC), Lymphocyte Cell Biology Unit, Laboratory of Genetics, Centre for Advanced Imaging, Psychiatry and Psychotherapy, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Statistics [Warwick], University of Warwick [Coventry], Osaka University [Osaka], Institute of Psychiatry, King’s College London, London SE5 8AF, UK, University of Calgary, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, University of California [Irvine] (UC Irvine), Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, Space and Naval Warfare Systems Center, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Department of Psychiatry, Division of Medical Psychology, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Développement et amélioration des plantes (UMR DAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Laboratory of Neuro Imaging [Los Angeles] (LONI), Departamento de Física Aplicada, Universidade de Vigo, Georgia State University, University System of Georgia (USG), Genentech, Inc. [San Francisco], Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Universiteit Leiden, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Department of Neurobiology, Care Sciences and Society, Karolinska Institutet [Stockholm], University of Manchester [Manchester], The University of Tennessee Health Science Center [Memphis] (UTHSC), iangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China, Centre for Ultrahigh Bandwidth Devices for Optical Systems (CUDOS), Macquarie University, Cognitive Neuroscience Laboratory (CNL), Harvard University, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], 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], Division of Molecular and Cellular Therapeutics, Scottish Association for Marine Science (SAMS), Structural Biology Laboratory, Department of Chemistry, University of York, Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, 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), Deparment of Medical Genetics, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], Institute for Community Medicine, Department Epidemiology of Health Care and Community Health, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig-Universität Leipzig, Institute of Clinical Chemistry and Laboratory Medicine, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), Stanley Center for Psychiatric Research, 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], Psychiatric and Neurodevelopmental Genetics Unit, 849 Department of Human Genetics, Institute for Community Medicine, Institute for Energy Systems and Thermodynamics, Renyi Institute, Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam 3000 CB, The Netherlands, Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands, Vrije Universiteit Amsterdam [Amsterdam] (VU), Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Dept of Psychology, Laboratoire de Recherche Magellan, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut d'Administration des Entreprises (IAE) - Lyon, Institut de Socio-économie des Entreprises et des ORganisations (ISEOR), Institut de socio-économie des entreprises et des organisations, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Centre for Allergy Research, Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Medical University of Łódź (MUL), Psychiatry Institute, Department of Health and Human Services, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia = University of Perugia (UNIPG), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Australian Centre for Research into Injury in Sport and its Prevention, Monash University [Clayton], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, School of Psychology [Nottingham], University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), SickKids - The Hospital for sick children, European Centre for Medium-Range Weather Forecasts (ECMWF), University of Eastern Finland, Centre for Population Health Sciences, Lieber Institute for Brain Development [Baltimore] (LIBD), Johns Hopkins University (JHU), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria, Austrian Institute of Technology [Vienna] (AIT), INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, INSERM, Neuroepidemiology U708, Bordeaux, France, Karlsruhe Institute of Technology (KIT), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Harvard Medical School [Boston] (HMS), Computer Science and Artificial Intelligence Laboratory [Cambridge] (CSAIL), Massachusetts Institute of Technology (MIT), University of Washington [Seattle], Department of Physics [Stockholm], Stockholm University, Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Boston University [Boston] (BU), 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), Faculty of Medicine, University of Iceland [Reykjavik], Icelandic Heart Association, Kopavogur, Iceland., Boston University School of Medicine (BUSM), Laboratoire d'Ingénierie des Matériaux de Bretagne (LIMATB), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of California-University of California, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Gènes, Synapses et Cognition, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), UE 1354 Unité d'expérimentation sur les Ruminants de Theix, Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Unité d'expérimentation sur les Ruminants de Theix (UE RT), Radboud university [Nijmegen], McGill University, University of Bergen (UIB), Universität Heidelberg [Heidelberg], Beijing Normal University, University of California, University of Bonn, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Neurosciences [San Diego], Department of Cognitive Sciences [San Diego], The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada, McGill University-McGill University, US 1367 MetaGénoPolis, Institut National de la Recherche Agronomique (INRA)-Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA)-MetaGénoPolis (MGP), Yale University School of Medicine, King Faisal Specialist Hospital and Research Centre, Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia, Department of Genomics, Life & Brain Center, University of Bonn, Bonn D-53127, Germany, University of Oxford [Oxford]-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], School of Psychology, University of Sussex, Brighton BN1 9QH, UK, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Department of Neurology [University of Calgary], Department of Clinical Neuroscience [University of Calgary], University of California [Irvine] (UCI), Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Universidate de Vigo, Harvard University [Cambridge], Radboud university [Nijmegen]-Radboud university [Nijmegen], Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Centre de Recherche Magellan, Institut d'Administration des Entreprises (IAE) - Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Università degli Studi di Perugia (UNIPG), 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, 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), Université de Bretagne Sud (UBS)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), The Alzheimer’s Disease Neuroimaging Initiative, The CHARGE Consortium, EPIGEN, IMAGEN, SYS, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital]-University of Oxford [Oxford], Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF), 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, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-FMRIB Centre, Neurology, Psychiatry, Anatomy and neurosciences, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Biological Psychology, Cognitive Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, EMGO+ - Mental Health, Child and Adolescent Psychiatry / Psychology, Epidemiology, Radiology & Nuclear Medicine, Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California, Los Angeles, California, USA, Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, MRC- SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK, Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany, Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany, Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands, Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK, Department of Computer Science, Lagos State University, Lagos, Nigeria, Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Heriot-Watt University [Edinburgh] ( HWU ), Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Unité d'expérimentation sur les Ruminants de Theix ( UE RT ), Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway, NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway, Montreal Neurological Institute [Montréal], NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen 5021, Norway, Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 ( PC2A ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands, International Max Planck Research School for Language Sciences, Nijmegen 6525 XD, The Netherlands, Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA, Department of Psychology, Yale University, New Haven, Connecticut 06511, USA, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA, University College of London [London] ( UCL ), Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA, Université de Bonn, Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands, Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK, Imperial College London-School of public health-MRC-HPA Centre for Environment and Health, Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid 28029, Spain, Institut Parisien de Chimie Moléculaire ( IPCM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Aging Research Center [Karolinska Institutet] ( ARC ), Max Planck Institute of Psychiatry, Munich 80804, Germany, Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, California 92093, USA, Department of Cognitive Sciences, University of California, San Diego, California 92161, USA, Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia, Department of Psychology, University of Oslo, Oslo 0373, Norway, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada, Molecular and Cellular Therapeutics, The Royal College of Surgeons, Dublin 2, Ireland, Institut National de la Recherche Agronomique ( INRA ) -MetaGénoPolis ( MGP ) -Microbiologie et Chaîne Alimentaire ( MICA ), UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK, Department of Medicine, Imperial College London, London W12 0NN, UK, Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK, Yale School of Medicine, Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA, University College Dublin [Dublin] ( UCD ), Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK, Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia, Centre épigénétique et destin cellulaire ( EDC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), School of public health-Tehran University of Medical Siences, University of New South Wales [Sydney] ( UNSW ), Texas Biomedical Research Institute, San Antonio, Texas 78245, USA, Institute of Neuroscience and Medicine ( INM-1 ), University of Basel ( Unibas ), Cambridge University, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA, University of Texas Health Science Center, San Antonio, Texas 78229, USA, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 20892, USA, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald 17475, Germany, University Medical Center Groningen, University of Groningen, University of Greifswald, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA, NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland 21201, USA, nstitute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK, Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland, Baltimore, Maryland 21201, USA, Department of Pathology and Cell Biology, Columbia University Medical Center, New York 10032, USA, Lymphocyte Cell Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA, University of Oslo ( UiO ) -Institute of Clinical Medicine-Oslo University Hospital, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo ( UiO ) -European Network of Bipolar Research Expert Centers (ENBREC) Group, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin 10117, Germany, Erasmus MC, Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIH), Bethesda, Maryland, USA, Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Central Institute of Mental Health, UMR 1098 Développement et Amélioration des Plantes, Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -MontpellierSupAgro ( MontpellierSupAgro ) -Génétique et amélioration des plantes ( G.A.P. ) -Développement et Amélioration des Plantes ( DAP ), Laboratory of Neuro Imaging [Los Angeles] ( LONI ), University of California at Los Angeles [Los Angeles] ( UCLA ), Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Genentech, South San Francisco, California 94080, USA, Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands, LUMC, Carver College of Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm SE-141 83, Sweden, Behavioral Epidemiology Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland 20892, USA, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK, Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA, Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA, Centre Interlangues - Texte, Image, Langage ( TIL ), Université de Bourgogne ( UB ), Centre for Ultrahigh Bandwidth Devices for Optical Systems ( CUDOS ), Icahn School of Medicine at Mount Sinai [New York], The Mind Research Network & LBERI, Albuquerque, New Mexico 87106, USA, Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA, Scottish Association for Marine Science ( SAMS ), Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels 1070, Belgium, National Institutes of Health ( NIH ) -National Institute of Mental Health (NIMH), Harvard Medical School [Boston] ( HMS ) -Massachusetts General Hospital [Boston], Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242, USA, Luleå University of Technology ( LUT ), Broad Institute of MIT and Harvard, Massachusetts General Hospital, Vrije Universiteit Amsterdam [Amsterdam] ( VU ), Université Jean Moulin - Lyon III-Institut d'Administration des Entreprises (IAE) - Lyon, Institut de Socio-économie des Entreprises et des ORganisations ( ISEOR ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Laboratoire d'Informatique de Grenoble ( LIG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan, Karolinska University Hospital (Solna), Medical University of Łódź ( MUL ), National Institutes of Health ( NIH ), University of Perugia, Commonwealth Scientific and Industrial Research Organisation, University Medical Center Utrecht-Brain Center Rudolf Magnus, University of Nottingham, UK ( UON ), McConnell Brain Imaging Centre ( MNI ), The Hospital for sick children [Toronto] ( SickKids ), Department of Medical and Molecular Genetics, King’s College London, London SE1 9RT, UK, European Centre for Medium-Range Weather Forecasts ( ECMWF ), Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA, Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, Austrian Institute of Technology [Vienna] ( AIT ), Karlsruhe Institute of Technology ( KIT ), General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA, Department of Radiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA, Computer Science and Artificial Intelligence Laboratory [Cambridge] ( CSAIL ), Massachusetts Institute of Technology ( MIT ), Department of Epidemiology, University of Washington, Seattle, Washington, USA, Department of Neurology, University of Washington, Seattle, Washington, USA, Department of Physics, Stockholm University ( Department of Physics, Stockholm University ), Université de Lille, Sciences Humaines et Sociales, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA, Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA, Groupe d'Imagerie Neurofonctionnelle ( GIN - UMR 5296 ), Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-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 ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université de Bordeaux ( UB ), Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA, Faculty of Medicine, University of Iceland, Reykjavik, Iceland, Department of Neurology, Boston University School of Medicine, Framingham Heart Study, Boston, MA, Department of Neurology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Laboratoire d'Ingénierie des Matériaux de Bretagne ( LIMATB ), Université de Bretagne Sud ( UBS ) -Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Université de Brest ( UBO ) -Université de Brest ( UBO ), King's College, Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, and Broad Institute of © 2012 Nature America, Inc. All rights reserved. Nature Ge N etics aDV a NCE ONLINE PUBLIC a TION 7 l e t t e r s Harvard and MIT, Cambridge, Massachusetts, US
Subjects: CHROMATIN, Male, Netherlands Twin Register (NTR), Aging, Identification, nervous-system, human geography, SEGMENTATION, Caudate nucleus, Apoptosis, Expression, Genome-wide association study, Striatum, Hippocampal formation, Hippocampus, BASAL GANGLIA, 130 000 Cognitive Neurology & Memory, Basal ganglia, genetics [Gene Expression Regulation, Developmental], Hippocampal, Child, anatomy & histology [Skull], Aged, 80 and over, Genetics, Sex Characteristics, KINECTIN, Genome-wide association, Multidisciplinary, Putamen, Brain, Gene Expression Regulation, Developmental, blood, brain, disease incidence, genetic variation, neurology, Organ Size, Human brain, Middle Aged, organization, Magnetic Resonance Imaging, genetics [Genetic Variation], Chromatin, Dynamics, genetics [Membrane Proteins], medicine.anatomical_structure, genetics [Aging], Anatomy & histology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Female, ddc:500, anatomy & histology [Caudate Nucleus], Neuroinformatics, EXPRESSION, Adult, Adolescent, Evolution, anatomy & histology [Hippocampus], ORGANIZATION, genetics [Genetic Loci], Biology, Article, Young Adult, SDG 3 - Good Health and Well-being, Journal Article, medicine, Humans, GENOME-WIDE ASSOCIATION, General, genetics [Apoptosis], Kinectin, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], HIPPOCAMPAL, IDENTIFICATION, genetics [Organ Size], [SCCO.NEUR]Cognitive science/Neuroscience, Skull, segmentation, Genetic Variation, Membrane Proteins, NERVOUS-SYSTEM, anatomy & histology [Putamen], Genetic Loci, KTN1 protein, human, Caudate Nucleus, anatomy & histology [Brain], Neuroscience, Genome-Wide Association Study
Abstract: Contains fulltext : 144426.pdf (Publisher’s version ) (Closed access) Contains fulltext : 144426pre.pdf (Author’s version preprint ) (Open Access) The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. 6 p.
Published: 2015
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12. Lysosomal impairment in Parkinson's disease

Author: Marta Martinez-Vicente, Benjamin Dehay, Zhenyue Yue, Mark R. Cookson, Kim A. Caldwell, Miquel Vila, Guy A. Caldwell, Christine Klein, Erwan Bezard, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases, Department of Biological Sciences (Alabama), University of Alabama [Tuscaloosa] (UA), Departments of Neurology and Neuroscience, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Software and System Architectures (Siemens AG Corporate Technology), Siemens AG [Munich], Department of Computer Science and Artificial Intelligence (DECSAI), University of Granada [Granada], Vall d’Hebron Research Institute (VHIR), University of Alabama at Birmingham [ Birmingham] (UAB), National Institutes of Health [Bethesda] (NIH), Universität zu Lübeck [Lübeck], Autonomous University of Barcelona, Catalan Institution for Research and Advanced Studies, Dehay, Benjamin, Universität zu Lübeck = University of Lübeck [Lübeck], and Universitat Autònoma de Barcelona (UAB)
Subjects: Parkinson's disease, [SDV]Life Sciences [q-bio], PINK1, Biology, Protein Serine-Threonine Kinases, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Neuroprotection, Parkin, Article, 03 medical and health sciences, 0302 clinical medicine, Lysosome, medicine, Autophagy, Animals, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Gaucher Disease, Neurodegeneration, Parkinson Disease, medicine.disease, LRRK2, Cell biology, [SDV] Life Sciences [q-bio], Proton-Translocating ATPases, medicine.anatomical_structure, Neurology, Biochemistry, Glucosylceramidase, Neurology (clinical), Lysosomes, Glucocerebrosidase, Protein Kinases, 030217 neurology & neurosurgery, Signal Transduction
Abstract: International audience; Impairment of autophagy-lysosomal pathways (ALPs) is increasingly regarded as a major pathogenic event in neurodegenerative diseases, including Parkinson's disease (PD). ALP alterations are observed in sporadic PD brains and in toxic and genetic rodent models of PD-related neurodegeneration. In addition, PD-linked mutations and post-translational modifications of α-synuclein impair its own lysosomal-mediated degradation, thereby contributing to its accumulation and aggregation. Furthermore, other PD-related genes, such as leucine-rich repeat kinase-2 (LRRK2), parkin, and phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), have been mechanistically linked to alterations in ALPs. Conversely, mutations in lysosomal-related genes, such as glucocerebrosidase (GBA) and lysosomal type 5 P-type ATPase (ATP13A2), have been linked to PD. New data offer mechanistic molecular evidence for such a connection, unraveling a causal link between lysosomal impairment, α-synuclein accumulation, and neurotoxicity. First, PD-related GBA deficiency/mutations initiate a positive feedback loop in which reduced lysosomal function leads to α-synuclein accumulation, which, in turn, further decreases lysosomal GBA activity by impairing the trafficking of GBA from the endoplasmic reticulum-Golgi to lysosomes, leading to neurodegeneration. Second, PD-related mutations/deficiency in the ATP13A2 gene lead to a general lysosomal impairment characterized by lysosomal membrane instability, impaired lysosomal acidification, decreased processing of lysosomal enzymes, reduced degradation of lysosomal substrates, and diminished clearance of autophagosomes, collectively contributing to α-synuclein accumulation and cell death. According to these new findings, primary lysosomal defects could potentially account for Lewy body formation and neurodegeneration in PD, laying the groundwork for the prospective development of new neuroprotective/disease-modifying therapeutic strategies aimed at restoring lysosomal levels and function.
Published: 2013
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13. Depression and Diet Quality, US Adolescents and Young Adults: National Health and Nutrition Examination Survey, 2015-March 2020.

Author: Ogden CL, Ansai N, Fryar CD, Wambogo EA, and Brody DJ
Subjects: Humans, Adolescent, Male, Female, Young Adult, United States epidemiology, Cross-Sectional Studies, Adult, Child, Diet statistics & numerical data, Prevalence, Nutrition Surveys, Depression epidemiology, Diet, Healthy statistics & numerical data, Diet, Healthy psychology
Abstract: Background: Depression is a common mental health disorder., Objective: The objective of this study was to explore the association between diet quality, as measured by the Healthy Eating Index 2020 (HEI-2020), and depression symptoms among US adolescents and young adults aged 12 to 29 years., Design: The study design was a cross-sectional secondary data analysis., Participants: Data from the first 24-hour dietary recall for adolescents and young adults aged 12 to 29 years in the National Health and Nutrition Examination Survey from 2015 to March 2020 (n = 4750) were analyzed., Main Outcome Measure: Depression was defined as a score ≥10 on the Patient Health Questionnaire, reflecting moderate or severe symptoms in the previous 2 weeks., Statistical Analyses Performed: HEI-2020 total (range, 0-100) and component scores were calculated for those with and without depression. Predicted HEI-2020 scores were estimated from linear regression models, adjusting for age, gender, race and Hispanic origin, family income, and seeing a mental health professional in the past year. Statistical analyses accounted for the complex sample design., Results: The prevalence of depression among adolescents and young adults was 7.8% (95% CI 6.3% to 9.5%). Total HEI-2020 score was 45.9 (95% CI 45.0 to 46.7) out of 100 on a given day during 2015 to March 2020. Among young people with depression, total HEI-2020 score was lower than among those without depression (41.7 vs 46.2; P < .001). After adjustment for covariates, the difference was attenuated, but remained significant. In adjusted analyses, HEI-2020 component scores were lower for those with depression compared with those without depression for the adequacy components: total fruits (1.4 vs 1.7; P = .03), whole fruits (1.2 vs 1.7; P < .01), total vegetables (2.1 vs 2.6; P < .01), greens and beans (0.8 vs 1.2; P < .01), and total protein foods (3.6 vs 4.0; P = .02) out of a maximum score of 5. There were no statistically significant differences observed for whole grains, dairy, seafood and plant proteins, fatty acids, saturated fats, refined grains, sodium, or added sugars., Conclusions: Overall diet quality is low among young people. Diet quality, especially consumption of fruits, vegetables, and protein foods was lower among young people with depression compared with those without depression., (Published by Elsevier Inc.)
Published: 2025
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14. Effectiveness of electronic medical record-based strategies for death and hospital admission endpoint capture in pragmatic clinical trials.

Author: Rahafrooz M, Elbers DC, Gopal JR, Ren J, Chan NH, Yildirim C, Desai AS, Santos AA, Murray K, Havighurst T, Udell JA, Farkouh ME, Cooper L, Gaziano JM, Vardeny O, Mao L, Kim K, Gagnon DR, Solomon SD, and Joseph J
Subjects: Humans, United States, Heart Failure mortality, Heart Failure therapy, Pragmatic Clinical Trials as Topic, Electronic Health Records, Hospitalization, Algorithms
Abstract: Objective: Event capture in clinical trials is resource-intensive, and electronic medical records (EMRs) offer a potential solution. This study develops algorithms for EMR-based death and hospitalization capture and compares them with traditional event capture methods., Materials and Methods: We compared the effectiveness of EMR-based event capture and site-captured events adjudicated by a clinical endpoint committee in the multi-center INfluenza Vaccine to Effectively Stop cardio Thoracic Events and Decompensated heart failure (INVESTED) trial for participants from the Veterans Affairs healthcare system. Varying time windows around event dates were used to optimize events matching. The algorithms were externally validated for heart failure hospitalizations in the Medical Information Mart for Intensive Care (MIMIC)-IV database., Results: We observed 100% sensitivity for death events with a 1-day window. Sensitivity for cardiovascular, heart failure, pulmonary, and nonspecific cardiopulmonary hospitalizations using discharge diagnosis codes varied between 75% and 95%. Including Centers for Medicare & Medicaid Services data improved sensitivity with no meaningful decrease in specificity. The MIMIC-IV analysis showed 82% sensitivity and 99% specificity for heart failure hospitalizations., Discussion: EMR-based method accurately identifies all-cause mortality and demonstrates high accuracy for cardiopulmonary hospitalizations. This study underscores the importance of optimal time windows, data completeness, and domain variability in EMR systems., Conclusion: EMR-based methods are effective strategies for capturing death and hospitalizations in clinical trials; however, their effectiveness may be influenced by the complexity of events and domain variability across different EMR systems. Nonetheless, EMR-based methods can serve as a valuable complement to traditional methods., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2024.)
Published: 2025
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15. Optimizing Exposure Measures in Large-Scale Household Air Pollution Studies: Results from the Multicountry HAPIN Trial.

Author: Steenland K, Pillarisetti A, Johnson M, Rosenthal J, Balakrishnan K, Underhill L, Thompson L, McCracken J, Waller L, Nicolaou L, Clark M, Checkley W, Peel J, and Clasen T
Subjects: Humans, Infant, Female, Particulate Matter analysis, Environmental Exposure, Carbon Monoxide analysis, Air Pollutants analysis, Cooking, Family Characteristics, Adult, Environmental Monitoring methods, Mothers, Air Pollution, Indoor analysis
Abstract: Repeated measurements of household air pollution may provide better estimates of average exposure but can add to costs and participant burden. In a randomized trial of gas versus biomass cookstoves in four countries, we took supplemental personal 24-h measurements on a 10% subsample for mothers and infants, interspersed between protocol samples. Mothers had up to five postrandomization protocol measurements over 16 months, while infants had three measurements over one year. For the subsample, we added up to 6 supplemental postrandomization samples for mothers and 3 for infants, measuring PM 2.5 , black carbon (BC) (mothers only), and carbon monoxide (CO) at each visit. 310 mothers had both protocol ( n = 1026) and supplemental ( n = 1099) valid exposure measurements. For children, supplemental data sufficient for analysis were collected in only two countries; 94 infants had both protocol ( n = 317) and supplemental ( n = 234) samples. The geometric means for protocol and supplemental samples for mothers for PM 2.5 were 37 μg/m 3 and 38 μg/m 3 , respectively, while for infants, they were 42 μg/m 3 and 46 μg/m 3 . Mixed models comparing supplemental to protocol samples, controlling for covariates, found few differences between protocol and supplemental samples. Supplemental analyses among control mothers with complete protocol measurements found that an average of three measurements explained 81% of the variance of the average of all six measurements.
Published: 2025
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16. TP53 Mutant Variant Allele Frequency and Cytogenetics Determine Prognostic Groups in MDS/AML for Transplantation.

Author: Lontos K, Saliba RM, Kanagal-Shamanna R, Ozcan G, Ramdial JL, Chen GL, Kadia TM, Short NJ, Daver NG, Kantarjian HM, Marin D, Kebriaei P, Popat UR, Champlin RE, Shpall EJ, and Oran B
Abstract: Results following hematopoietic stem cell transplantation (HSCT) for TP53-mutated myeloid malignancies are disappointing. Several HSCT centers decline to perform HSCT for patients with TP53 mutation because of poor outcomes. In this study, we analyzed 240 patients with TP53-mutated myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) that underwent HSCT. We aimed to identify the patients that benefit most from HSCT. The primary outcome was progression-free survival (PFS). Fifty-two percent of the cohort had AML and the median age of the cohort was 62. AML and MDS outcomes were similar. We identified several favorable prognostic factors for PFS including the absence of complex cytogenetics/5q deletion/7q deletion, a lower variant allele frequency (VAF), a mono-hit status and the use of a matched-related donor. Using classification and regression tree analysis, we identified VAF and cytogenetics as the two most important prognostic factors. Patients with TP53mut VAF ≥ 50% had a 2-year PFS of 3%, patients with TP53mut VAF < 50% and complex/5q/7q cytogenetics abnormalities had 2-year PFS of 22%. Patients with TP53mut VAF < 50% and without complex/5q/7q cytogenetics had 2-year PFS of 60%. This data informs clinical practice and helps patients decide whether to pursue HSCT., (Copyright © 2025 American Society of Hematology.)
Published: 2025
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17. Examining the moderation of the relationship between socio-economic status and consumption intentions by food information labels.

Author: Pink AE, Stylianou KS, Lee L, Jolliet O, and Cheon BK
Abstract: Front-of-package-labelling needs to portray health and/or sustainability information effectively to all consumers in a way that is both effective and equitable. There is mixed evidence for the effectiveness of such labels based on socioeconomic status (SES). Framing health consequences in an intuitive manner could help to reduce disparities in label comprehension across SES. We examined whether the relationships of SES (objective and subjective) with perceived healthiness and environmental friendliness of foods is moderated by the presentation of food label information. We also examined intentions to change consumption as an outcome. Participants (N = 901, age: M = 46.62 years) from the USA completed the study online. Participants were randomly assigned to view either no information (control), standard nutrition facts (nutrition), HENI scores (health), carbon footprint scores (environment), or both HENI and carbon footprint scores (combined). Participants rated 24 foods on their perception of healthiness, environmental friendliness, and intentions to increase/decrease consumption. There was no consistent interaction effect between SES and food labels on perceived healthiness or environmental friendliness. There were also no consistent interactions of SES and food labels on intentions to change consumption. However, participants reporting higher subjective SES reported greater intentions to increase consumption of foods, regardless of their health or carbon footprint status. Overall, this preliminary research shows promise for HENI and environmental food labels as an intuitive method for portraying health and environmental information regardless of socioeconomic position., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)
Published: 2025
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18. Microglial NLRP3-gasdermin D activation impairs blood-brain barrier integrity through interleukin-1β-independent neutrophil chemotaxis upon peripheral inflammation in mice.

Author: Yoon SH, Kim CY, Lee E, Lee C, Lee KS, Lee J, Park H, Choi B, Hwang I, Kim J, Kim TG, Son J, Hyun YM, Hong S, and Yu JW
Subjects: Animals, Mice, Intracellular Signaling Peptides and Proteins metabolism, Intracellular Signaling Peptides and Proteins genetics, Mice, Inbred C57BL, Mice, Knockout, Inflammasomes metabolism, Matrix Metalloproteinases metabolism, Male, Neutrophil Infiltration drug effects, Receptors, Interleukin-8B metabolism, Neuroinflammatory Diseases metabolism, Neuroinflammatory Diseases immunology, Gasdermins, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Blood-Brain Barrier metabolism, Blood-Brain Barrier drug effects, Interleukin-1beta metabolism, Neutrophils metabolism, Neutrophils immunology, Microglia metabolism, Microglia drug effects, Phosphate-Binding Proteins metabolism, Lipopolysaccharides, Inflammation metabolism, Inflammation pathology
Abstract: Blood-brain barrier (BBB) disintegration is a key contributor to neuroinflammation; however, the biological processes governing BBB permeability under physiological conditions remain unclear. Here, we investigate the role of NLRP3 inflammasome in BBB disruption following peripheral inflammatory challenges. Repeated intraperitoneal lipopolysaccharide administration causes NLRP3-dependent BBB permeabilization and myeloid cell infiltration into the brain. Using a mouse model with cell-specific hyperactivation of NLRP3, we identify microglial NLRP3 activation as essential for peripheral inflammation-induced BBB disruption. Conversely, NLRP3 and microglial gasdermin D (GSDMD) deficiency markedly attenuates lipopolysaccharide-induced BBB breakdown. Notably, IL-1β is not required for NLRP3-GSDMD-mediated BBB disruption. Instead, microglial NLRP3-GSDMD axis upregulates CXCL chemokines and matrix metalloproteinases around BBB via producing GDF-15, promoting the recruitment of CXCR2-containing neutrophils. Inhibition of neutrophil infiltration and matrix metalloproteinase activity significantly reduces NLRP3-mediated BBB impairment. Collectively, these findings reveal the important role of NLRP3-driven chemokine production in BBB disintegration, suggesting potential therapeutic targets to mitigate neuroinflammation., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)
Published: 2025
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19. Illuminating the Invisible: Harnessing Low-dose Ultra-high-Resolution PCD-CT for Enhanced Visceral Artery Visualization.

Author: Abbaspour E, Pourmorteza A, Malayeri AA, and Nezami N
Abstract: Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nariman Nezami reports a relationship with MedStar Georgetown University Hospital that includes: employment. Nariman Nezami reports a relationship with Boston Scientific Corporation that includes consulting or advisory, speaking and lecture fees, and travel reimbursement. Nariman Nezami reports a relationship with Radiology Journal that includes board membership. Nariman Nezami reports a relationship with Microbot Medical that includes consulting or advisory and equity or stocks. Nariman Nezami is the owner of IRAD Graphics and Info Med Solutions. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Published: 2025
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20. How I Treat Higher-Risk MDS.

Author: Mina A and Komrokji RS
Abstract: Myelodysplastic syndromes/neoplasms (MDS) are a widely heterogenous group of myeloid malignancies characterized by morphologic dysplasia, a defective hematopoiesis, and recurrent genetic abnormalities. The original and revised International Prognostic Scoring Systems (IPSS) have been used to risk-stratify patients with MDS to guide treatment strategies. In higher-risk MDS, the therapeutic approach is geared toward delaying leukemic transformation and prolonging survival. For over a decade, the hypomethylating agents azacitidine and decitabine have been the standard of care and, when feasible, an allogeneic hematopoietic stem cell transplantation (AHSCT) should be considered. However, the IPSS scoring systems solely rely on clinical, morphological, and cytogenetic features and do not account for somatic mutations present in over 80% of cases. These genetic abnormalities have been shown to play a crucial role in prognostication, prompting the development of molecular IPSS, and the integration of genomic features into MDS classification systems in recent years. In this review, we delineate our approach to higher-risk MDS in the context of updated classifications and the latest prognostication tools. We employ illustrative clinical cases to support our discussion and share insights from recent clinical trials, highlighting lessons learned., (Copyright © 2025 American Society of Hematology.)
Published: 2025
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21. Evaluation of Intestinal Permeability Using Serum Biomarkers in Learning Early About Peanut Allergy Trial.

Author: Aktas ON, Mateja A, Li MJ, Chatman L, Grieco MC, Baloh CH, Huffaker M, Wheatley LM, du Toit G, Lack G, Brittain E, and Frischmeyer-Guerrerio PA
Abstract: Background: Intestinal barrier dysfunction may lead to a break in tolerance and development of food allergy (FA). There is contradictory evidence on whether intestinal permeability (IP) is altered in IgE-mediated FA. Thus, we sought to determine whether IP differed between children with eczema who did (FA group) or did not (atopic controls, ACs) develop FA and whether peanut sensitization, allergy, and early introduction impacted IP using serum biomarkers zonulin, soluble CD14, and Intestinal Fatty Acid Binding Protein among randomly selected participants enrolled in the Learning Early About Peanut allergy trial., Methods: FA group was defined as having at least one FA at either baseline (4-11 months) or 60 months of age (V60). ACs had eczema at baseline and no FA at either visit. Serum IP markers (sIPMs) were measured by ELISA at baseline and V60, and their relationship with the clinical characteristics of participants was analyzed using parametric tests and linear regression models., Results: We evaluated 237 FA subjects and 76 ACs. sIPM levels were similar in FA subjects and ACs at baseline and V60. Age when the child first developed any FA (< 1 year vs. > 1 year), eczema severity, peanut sensitization, peanut allergy, and early peanut introduction were not statistically significantly associated with sIPM levels. Total IgE and eosinophil levels, peanut-specific IgE, IgG4, and IgG4/IgE ratio were not correlated with sIPM levels., Conclusions: No differences in sIPMs were detected to support altered IP in infants with FA compared to ACs or following early peanut introduction among peanut-sensitized children., (© 2025 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)
Published: 2025
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22. SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocols.

Author: Ursino M, Villacampa G, Rekowski J, Dimairo M, Solovyeva O, Ashby D, Berlin J, Boix O, Calvert M, Chan AW, Coschi CH, Evans TRJ, Garrett-Mayer E, Golub RM, Guo C, Hayward KS, Hopewell S, Isaacs JD, Ivy SP, Jaki T, Kholmanskikh O, Kightley A, Lee S, Liu R, Mander A, Marshall LV, Matcham J, Patel D, Peck R, Rantell KR, Richards DP, Rouhifard M, Seymour L, Tanaka Y, Weir CJ, de Bono J, and Yap C
Abstract: Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity. To address this gap, the international consensus-driven SPIRIT-DEFINE checklist was developed through a robust methodological framework for guideline development, with the aim to improve completeness and clarity in EPDF trial protocols. The checklist builds on the SPIRIT statement, adding 17 new items and modifying 15 existing ones.The SPIRIT-DEFINE explanation and elaboration (E&E) document provides comprehensive information to enhance understanding and usability of the SPIRIT-DEFINE checklist when writing an EPDF trial protocol. Each new or modified checklist item is accompanied by a detailed description, its rationale with supportive evidence, and examples of good reporting curated from EPDF trial protocols covering a range of therapeutic areas and interventions. We recommend utilising this paper alongside the SPIRIT statement, and any relevant extensions, to enhance the development and review of EPDF trial protocols.By facilitating adoption of the SPIRIT-DEFINE statement for EPDF trials, this E&E document can promote enhancement of methodological rigour, patient safety, transparency, and facilitate the generation of high-quality, reproducible evidence that will strengthen the foundation of early phase research and ultimately improve patient outcomes., Funding: This work is a further extension of the SPIRIT-DEFINE study, which obtained no external funding. The principal investigator (CY) used internal staff resources, together with additional resources from external partners, to conduct this study. The SPIRIT-DEFINE study is a component of the DEFINE project, which also developed the MRC/NIHR funded CONSORT-DEFINE guidance. ICR-CTSU receives programmatic infrastructure funding from Cancer Research UK (C1491/A25351; CTUQQR-Dec22/100004), which has contributed to accelerating the advancement and successful completion of this work., Competing Interests: Example 1“An internal monitoring committee (IMC) will monitor patient safety throughout the study. The IMC will include Sponsor representatives from Clinical Science, Drug Safety, Biostatistics, and Statistical Programming and Analysis. In addition to the ongoing assessment of the incidence and nature of adverse events (particularly Grade 3 events), SAEs, deaths, and laboratory abnormalities performed by the investigator and the Medical Monitor, the IMC will review data supporting the determination of the recommended phase 2 dose (RP2D) and then, at regular intervals during the expansion phase. At the time of each review, the IMC will make appropriate recommendations (e.g., the study should continue as planned, additional analyses should be performed, enrollment should be held pending further safety evaluations). Decisions will be made in consideration of the totality of the available data. Ad hoc meetings may be called in addition to scheduled meetings, as necessary, to provide recommendations on management of any potential new safety signals.”106Example 2“For Part A, the safety review committee (SRC) will be comprised by a sponsor medical representative, the Medical Monitor, a sponsor-independent investigator, and a site representative. For the decision to progress to Part B, an independent statistical consultant and a third party expert will also be included. Key roles of the SRC are as follows:-Before progression to the next cohort, assess the data, decide whether to approve initiation of the next cohort/dose level and to confirm the planned dose or define another dose for use. The data assessed by the SRC is defined in Section 1.1.-After completing its evaluation of the 48 h data for the first 6 subjects per group in cohort, the SRC may request a prolongation of the observation period to up to Day 7 data for later cohorts or other similar adaptions to protect subject wellbeing.-Throughout the trial, assess whether to replace trial subjects permanently discontinued due to safety issues.-Throughout the trial, approval from the SRC will be required prior to resuming any dosing in a “stopped” cohort (see Section 6.6.1). The SRC may call for the opening of a lower dose level cohort.-SRC may make recommendations on increasing the length of the observation periods and additional subject wellbeing calls may be included at the discretion of the SRC. The SRC will act according to its own written procedures described in a charter, and will prepare written minutes of its meetings.”107Example 3“The SMC [Safety Monitoring Committee] is an independent group of at least 3 experts that monitors subject safety and advises DMID [Sponsor]. SMC members will be separate and independent of study staff participating in this trial and should not have scientific, financial, or other conflicts of interest related to this trial. The SMC will consist of members with appropriate expertise to contribute to the interpretation of data from this trial. A quorum will consist of a simple majority. The SMC will hold an organizational meeting prior to enrollment. At this meeting, the SMC will review the charter, protocol, ICF, and safety report template. […] Procedures for SMC reviews/meetings will be defined in the SMC charter. The SMC will review applicable data, including, but not limited to, enrollment, demographics, dosing data, clinical laboratory data, and safety data, at scheduled timepoints during this trial as defined in the SMC charter. The SMC will review blinded aggregate data in the open session of the SMC meetings.”108ExplanationFor EPDF trials, with their focus on risk of harm, their characteristically adaptive nature, and a high number of possible interim analyses, it is key to be transparent in describing who will be involved in decision-making and, if possible, detail how decisions are made. The decision-making committee/group typically involves members with relevant specialist expertise to assess an EPDF trial, including clinical (and pharmacological and toxicological, depending on the intervention) experience,109 who may not necessarily be independent from the sponsor.110 Extensive information on the backgrounds of the committee/group members will increase the trial's credibility and reassure that the decision-making committee/group acts in the best interest of the trial participants. Authors should specify the composition of any decision-making committee/group who will review key outcomes, including safety and treatment tolerability, and make or recommend decisions (e.g., dose escalation/de-escalation, dose expansion, progression to another phase, stopping the trial early for futility). Such groups are sometimes referred to as a safety review committee/group, dose escalation committee/group, data (safety) monitoring committee or board, or similar. Details should include a summary of the role and reporting structure of the decision-making committee/group. A statement should be included addressing whether the decision-making committee/group is independent from the sponsor, funder, or trial team, and any competing interests should be described. Reference should be given to where further details, such as a decision-making committee charter, can be found, if not in the protocol.MU reports personal fees from PTC Therapeutics International Ltd., personal fees from ImCheck Therapeutics, grants and personal fees from eXYSTAT, personal fees from Saryga, grants from Sanofi, other from Novartis, other from Roche, outside the submitted work; GV reports personal fees from Pfizer, MSD, GSK, Pierre Fabrer and AstraZeneca, outside the submitted work; MD reports non-financial support from Sheffield Clinical Trials Research Unit during the conduct of the study; JB reports personal fees from Amplia, Astellas, Bayer, Nested, Mekanistic, Mirati, Merck, Oxford Biotherapeutics, Insmed, Merus, grants from AbbVie, Astellas, Atreca, Dragonfly, I-Mab, Incyte, Eli Lilly, BMS, Bayer, Pfizer, Sumitomo Dainippon Pharma Oncology, Tyra, Totus, 23 and me, Hibercell, Incendia, NCI, Ribosciences, grants and personal fees from Astra-Zeneca, personal fees from Novocure, from Boehringer-Ingelheim, outside the submitted work; OB reports personal fees from Bayer AG, outside the submitted work; MC reports grants from NIHR, UKRI, UK Research and Innovation, Merck, outside the submitted work; TRJE reports grants, non-financial support and other from Astra Zeneca, grants and other from Bayer, Bicycle Therapeutics, Bristol-Myers Squibb, grants from Celgene, grants and other from Medivir, Eisai, grants, personal fees and other from MSD, Nucana, Roche, grants and other from Seagen, grants from Adaptimmune, grants from Astellas, Avacta, Basilea, Beigene, Codiak, CytomX, Immunocore, iOnctura, GSK, Johnson & Johnson, Novartis, MiNa Therapeutics, Lilly, Nurix, Sanofi, Sapience, Starpharma, Sierra, T3P, UCB, Verastem, other from Ascelia, Genmab, grants and other from CV6, other from Chugai, grants from Pfizer, Amgen, BioNTech, Exelexis, Moderna, personal fees from British Journal of Cancer, non-financial support from Immodulon, outside the submitted work; KH reports grants from National Health and Medical Research Council of Australia, outside the submitted work; OK reports the views and opinions expressed in this publication are those of the individual co-authors and may not be understood or quoted as being made on behalf of or reflecting the position of any organisation, committee, working party or group with which the co-authors are affiliated; LM reports personal honorarium from Bayer, personal fees from Eisai, Merck, LifeArc Strategic Advisory Board, unpaid role for Children with Cancer UK Scientific Advisory Board, as ACCELERATE Steering Committee member, ITCC Solid Tumour Steering Committee member, ITCC Industry Strategy Committee member, ECMC Paediatric Network Deputy Lead; RP is an employee and a stockholder in F Hoffmann la Roche; DR reports other from various pharma companies, outside the submitted work; YT has received speaking fees and/or honoraria from Abbvie, Eisai, Chugai, Eli-Lilly, Behringer-Ingelheim, GlaxoSmithKline, Taisho, AstraZeneca, Daiichi-Sankyo, Gilead, Pfizer, UCB, Asahi-kasei, Astellas, received research grants from Behringer-Ingelheim, Taisho, Chugai; CJW reports grants from MRC-NIHR Methodology Research Programme Grant Ref: MR/T044934/1, during the conduct of the study; JSdB reports personal fees from Abbvie, Acai Therapeutics, Amgen, Astellas, Amunix, Bayer, Bioxcel Therapeutics, Celcuity, grants and personal fees from Crescendo, personal fees from Daiichi, Dark Blue Therapeutics, Duke Street Bo Ltd, Dunad Therapeutics, Endeavor Biomedicines INC, grants and personal fees from Genentech/Roche, other from GSK, personal fees from Macrogenics, grants and personal fees from Merck Serono, grants and personal fees from MetaCurUm, personal fees from Moma, grants and personal fees from Myricx, personal fees and other from Novartis, grants and personal fees from Nurix Therapeutics, personal fees from Nuvation Bio, One Carbon Therapeutics Inc, grants and personal fees from Oncternal, Orion Pharma, personal fees from Page Therapeutics, grants and other from Pfizer, other from Takeda, Tango Therapeutics, personal fees from Tubulis GmbH, grants and personal fees from Sanofi, Immunic Therapeutics, outside the submitted work; in addition, JSdB has a patent DNA Damage repair inhibitors for treatment of Cancer licensed to AstraZeneca, and a patent 17-substituted steroids useful in cancer treatment licensed to Janssen; CY reports grants from Cancer Research UK and Experimental Cancer Medicine Centres during the conduct of the study, personal fees from Faron Pharmaceuticals, Bayer and Merck, outside the submitted work. The other authors have no conflicts of interest to declare., (© 2024 The Author(s).)
Published: 2025
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23. CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.

Author: Rekowski J, Guo C, Solovyeva O, Dimairo M, Rouhifard M, Patel D, Alger E, Ashby D, Berlin J, Boix O, Calvert M, Chan AW, Coschi CH, de Bono J, Evans TRJ, Garrett-Mayer E, Golub RM, Hayward KS, Hopewell S, Isaacs JD, Ivy SP, Jaki T, Kholmanskikh O, Kightley A, Lee S, Liu R, Maia I, Mander A, Marshall LV, Matcham J, Peck R, Rantell KR, Richards DP, Seymour L, Tanaka Y, Ursino M, Weir CJ, and Yap C
Abstract: Early phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete. The international consensus-based CONSORT-DEFINE (Consolidated Standards for Reporting Trials Dose-finding Extension) statement, an extension of the CONSORT statement for randomised trials, was developed to improve the reporting of EPDF trials. The CONSORT-DEFINE statement introduced 21 new items and modified 19 existing CONSORT items.This CONSORT-DEFINE Explanation and Elaboration (E&E) document provides important information to enhance understanding and facilitate the implementation of the CONSORT-DEFINE checklist. For each new or modified checklist item, we provide a detailed description and its rationale with supporting evidence, and present examples from EPDF trial reports published in peer-reviewed scientific journals. When reporting the results of EPDF trials, authors are encouraged to consult the CONSORT-DEFINE E&E document, together with the CONSORT and CONSORT-DEFINE statement papers, and adhere to their recommendations. Widespread adoption of the CONSORT-DEFINE statement is likely to enhance the reporting quality of EPDF trials, thus facilitating the peer review of such studies and their appraisal by researchers, regulators, ethics committee members, and funders., Funding: This work is a further extension of the CONSORT-DEFINE study, which was funded by the UK Medical Research Council (MRC)-National Institute for Health and Care Research (NIHR) Methodology Research Programme (MR/T044934/1). The Clinical Trials and Statistics Unit at The Institute of Cancer Research (ICR-CTSU) receives programmatic infrastructure funding from Cancer Research UK (C1491/A25351; CTUQQR-Dec 22/100 004), which has contributed to accelerating the advancement and successful completion of this work., Competing Interests: Example 1“We started with a once a day schedule and allowed for exploration of other dosing schedules according to the decision of the Safety Monitoring Committee (consisting of all principal investigators, the sponsor's medical and safety officers, and an independent expert, who made all decisions regarding patient safety, dose-limiting toxicity (DLT) qualification, dose escalation, and recommended dose definition).”148 This example addresses the composition of the decision making or safety review committee or group but lacks the reporting structure. Example 2“Prior to dosing of the next cohort, the Data Monitoring Committee (DMC), which included two independent clinicians with expertise in immunology/rheumatology and coagulopathies, reviewed blinded safety data from dosing to 14 days and PK [pharmacokinetics] data from at least seven days after the last administered dose within the previous dose cohort.”149 This example addresses the composition of the decision making or safety review committee or group but lacks the reporting structure. Example 3“The Data Monitoring Committee reviewed all available data and evaluated newly emergent safety data including dose-limiting toxicity and provided the Sponsor Safety Committee with recommendations for the next dose level.”54 This example addresses the reporting structure but lacks the composition of the decision making or safety review committee or group. ExplanationEPDF trials typically include frequent interim reviews of accumulated key outcome data and analyses to inform interim decisions, particularly on safety and dose adaptations. The decision-making committee/group typically involves members with relevant specialist expertise to assess an EPDF trial, including clinical (and pharmacological and toxicological, depending on the intervention) experience,150 who may not necessarily be independent from the sponsor.151 It is helpful to specify the composition of people who make decisions in EPDF trials, as their expertise and perspectives can influence the conduct and interpretation of results. Moreover, as the type and composition of decision-making groups vary across different trials, the provision of detailed information may increase transparency, enhance the trial's data credibility, and help readers assess potential biases. Details on the composition of any decision-making committee/group that reviewed key outcomes, such as safety and treatment tolerability, and made or recommended decisions (including dose (de-)escalation, dose expansion, or progression to another phase); summary of its role and reporting structure (see Example 3); and a statement on whether it is independent from the sponsor, funder, or trials team (see Example 1 and Example 2) and competing interests should be provided. It can be helpful to provide a reference to where further details, such as a charter, can be found if they are not in the report. Such an oversight committee/group in EPDF trials could be an individual or a group of members and is sometimes referred to as the safety review committee/group, the dose escalation committee/group, or the data (safety) monitoring committee or board.MD reports a research grant from the UK Medical Research Council (MRC) and the National Institute for Health and Care Research (NIHR) Methodology Research Programme (MR/T044934/1) that supported the conduct of the study; JB reports personal fees from Mirati, Insmed, EMD Serono, Ipsen, Merck, Sharp, Dohme, Merus, Bms, Bexion (unpaid), Mekanistic, Agenus (pending), Astellas, Amplia, grants from Abbvie, Astellas, Atreca, Bayer, Dragonfly, I-Mab, Lilly, Incyte, EMD Serono, Pfizer, BMS, Tyra, Totus, Sumitomo Dainippon Pharma Oncology, 23 and me, parthenon/Incendia, Hibercell, Ribosciences, NCI, personal fees from Astra Zeneca, Novocure, Boehringer-Ingelheim, outside the submitted work; OB reports personal fees from Bayer AG, outside the submitted work; MC reports grants from NIHR, UKRI, UK Research and Innovation, Merck, outside the submitted work; JdB reports personal fees from Abbvie, Acai Therapeutics, Amgen, Astellas, Amunix, Bayer, Bioxcel Therapeutics, Celcuity, grants and personal fees from Crescendo, personal fees from Daiichi, Dark Blue Therapeutics, Duke Street Bio Ltd, Dunad Therapeutics, Endeavor Biomedicines INC, grants and personal fees from Genentech/Roche, other from GSK, personal fees from Macrogenics, grants and personal fees from Merck Serono, grants and personal fees from MetaCurUm, personal fees from Moma, grants and personal fees from Myricx, personal fees and other from Novartis, grants and personal fees from Nurix Therapeutics, personal fees from Nuvation Bio, One Carbon Therapeutics Inc, grants and personal fees from Oncternal, Orion Pharma, personal fees from Page Therapeutics, grants and other from Pfizer, other from Takeda, Tango Therapeutics, personal fees from Tubulis GmbH, grants and personal fees from Sanofi, Immunic Therapeutics, outside the submitted work; in addition, JdB has a patent DNA Damage repair inhibitors for treatment of Cancer licensed to AstraZeneca, and a patent 17-substituted steroids useful in cancer treatment licensed to Janssen; TRJE reports grants, non-financial support and other from Astra Zeneca, grants and other from Bayer, Bicycle Therapeutics, Bristol-Myers Squibb, grants from Celgene, grants and other from Medivir, Eisai, grants, personal fees and other from MSD, Nucana, Roche, grants and other from Seagen, grants from Adaptimmune, grants from Astellas, Avacta, Basilea, Beigene, Codiak, CytomX, Immunocore, iOnctura, GSK, Johnson & Johnson, Novartis, MiNa Therapeutics, Lilly, Nurix, Sanofi, Sapience, Starpharma, Sierra, T3P, UCB, Verastem, other from Ascelia, Genmab, grants and other from CV6, other from Chugai, grants from Pfizer, Amgen, BioNTech, Exelexis, Moderna, personal fees from British Journal of Cancer, non-financial support from Immodulon, outside the submitted work; KH reports grants from National Health and Medical Research Council of Australia, outside the submitted work; OK reports the views and opinions expressed in this publication are those of the individual co-authors and may not be understood or quoted as being made on behalf of or reflecting the position of any organisation, committee, working party or group with which the co-authors are affiliated; LM reports personal honorarium from Bayer, personal fees from Eisai, Merck, LifeArc Strategic Advisory Board, unpaid role for Children with Cancer UK Scientific Advisory Board, as ACCELERATE Steering Committee member, ITCC Solid Tumour Steering Committee member, ITCC Industry Strategy Committee member, ECMC Paediatric Network Deputy Lead; RP is an employee and a stockholder in F Hoffmann la Roche; DR reports other from various pharma companies, outside the submitted work; YT has received speaking fees and/or honoraria from Abbvie, Eisai, Chugai, Eli-Lilly, Boehringer-Ingelheim, GlaxoSmithKline, Taisho, AstraZeneca, Daiichi-Sankyo, Gilead, Pfizer, UCB, Asahi-kasei, Astellas, received research grants from Boehringer-Ingelheim, Taisho, Chugai; MU reports personal fees from PTC Therapeutics International Ltd., personal fees from ImCheck Therapeutics, grants and personal fees from eXYSTAT, personal fees from Saryga, grants from Sanofi, other from Novartis, other from Roche, outside the submitted work; CJW reports grants from MRC-NIHR Methodology Research Programme Grant Ref: MR/T044934/1, during the conduct of the study; CY reports grants from Medical Research Council (MRC), Cancer Research UK and Experimental Cancer Medicine Centres, during the conduct of the study, personal fees from Faron Pharmaceuticals, Bayer and Merck, outside the submitted work. The other authors have no conflicts of interest to declare., (© 2024 The Author(s).)
Published: 2025
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24. Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.

Author: Sun Y, Jenkins LM, El Touny LH, Zhu L, Yang X, Jo U, Escobedo L, Maity TK, Saha LK, Uribe I, Saha S, Takeda S, Leung AKL, Cheng K, and Pommier Y
Subjects: Humans, DNA Damage, Flap Endonucleases metabolism, Flap Endonucleases genetics, DNA Repair, Poly (ADP-Ribose) Polymerase-1 metabolism, DNA metabolism, ADP-Ribosylation, DNA Topoisomerases, Type II metabolism, Formaldehyde metabolism
Abstract: DNA-protein cross-links (DPCs) are among the most detrimental genomic lesions. They are ubiquitously produced by formaldehyde (FA), and failure to repair FA-induced DPCs blocks chromatin-based processes, leading to neurodegeneration and cancer. The type, structure, and repair of FA-induced DPCs remain largely unknown. Here, we profiled the proteome of FA-induced DPCs and found that flap endonuclease 1 (FEN1) resolves FA-induced DPCs. We revealed that FA also damages DNA bases adjoining the DPCs, leading to DPC-conjugated 5' flap structures via the base excision repair (BER) pathway. We also found that FEN1 repairs enzymatic topoisomerase II (TOP2)-DPCs. Furthermore, we report that both FA-induced and TOP2-DPCs are adenosine diphosphate (ADP) ribosylated by poly(ADP-ribose) polymerase 1 (PARP1). PARylation of the DPCs in association with FEN1 PARylation at residue E285 is required for the recruitment of FEN1. Our work unveils the identity of proteins forming FA-induced DPCs and a previously unrecognized PARP1-FEN1 nuclease pathway repairing both FA- and TOP2-DPCs.
Published: 2025
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25. Efficacy of cartilage-targeted IGF-1 in a mouse model of growth hormone insensitivity.

Author: Tailor K, van Ree J, Stowe T, Ventura B, Sisk C, Courtis J, Camp A, Elzamzami F, van Deursen J, O'Brien R, Baron J, and Lui JC
Subjects: Animals, Mice, Growth Plate drug effects, Growth Plate metabolism, Laron Syndrome drug therapy, Laron Syndrome metabolism, Male, Humans, Human Growth Hormone analogs & derivatives, Human Growth Hormone pharmacology, Female, Recombinant Fusion Proteins pharmacology, Recombinant Fusion Proteins therapeutic use, Signal Transduction drug effects, Insulin-Like Growth Factor I metabolism, Mice, Inbred C57BL, Disease Models, Animal, Cartilage metabolism, Cartilage drug effects
Abstract: Recombinant human IGF-1 is used to treat severe primary IGF-1 deficiency, but this treatment requires twice-daily injection, often does not fully correct the growth deficit, and has important off-target effects. We therefore sought to target IGF-1 to growth plate cartilage by generating fusion proteins combining IGF-1 with single-chain human antibody fragments that target matrilin-3, a cartilage matrix protein. We previously showed that this cartilage-targeting IGF-1 fusion protein (CV1574-1) promoted growth plate function in a GH-deficient (lit) mouse model. Here, we studied CV1574-1 in a second mouse model, C57BL/6 wild-type mice treated with pegvisomant to induce GH resistance. In this model, once-daily injections of CV1574-1 for 5 days partially restored the pegvisomant-induced decrease in growth plate height without increasing kidney cell proliferation. Furthermore, we found that subcutaneous CV1574-1 showed significantly reduced hypoglycemic effect compared to injection of IGF-1 itself. Lastly, to gain mechanistic insights into the role of matrilin-3 targeting, we assessed the ability of CV1574-1 to activate AKT signaling in vitro and found that CV1574-1 caused a prolonged increase in AKT signaling compared to IGF-1 and that this effect was dependent on matrilin-3. Taken together, our findings provide further evidence that cartilage-targeted therapy could provide new pharmacological approaches for the treatment of childhood growth disorders, such as GH-insensitivity syndrome., Competing Interests: RO’B, TS, JR, BV, JD, and KT were employees of Cavalry Biosciences, Inc. and have a financial interest in CV1574-1 and related molecules. JB and JL are inventors of a patent licensed by Cavalry Biosciences, Inc. related to CV1574-1 and received research support for this work from Cavalry Biosciences, Inc. under a Cooperative Research and Development Agreement. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Tailor, van Ree, Stowe, Ventura, Sisk, Courtis, Camp, Elzamzami, van Deursen, O’Brien, Baron and Lui.)
Published: 2025
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26. Differential inclusion of NEB exons 143 and 144 provides insight into NEB-related myopathy variant interpretation and disease manifestation.

Author: Silverstein S, Orbach R, Syeda S, Foley AR, Gorokhova S, Meilleur KG, Leach ME, Uapinyoying P, Chao KR, Donkervoort S, and Bönnemann CG
Subjects: Humans, Male, Muscle, Skeletal pathology, Muscle, Skeletal metabolism, Muscular Diseases genetics, Muscular Diseases pathology, Mutation, Protein Isoforms genetics, Magnetic Resonance Imaging, Pedigree, Exons genetics, Muscle Proteins genetics
Abstract: Biallelic pathogenic variants in the gene encoding nebulin (NEB) are a known cause of congenital myopathy. We present two brothers with congenital myopathy and compound heterozygous variants (NC_000002.12:g.151692086G>T; NM_001271208.2: c.2079C>A; p.(Cys693Ter) and NC_000002.12:g.151533439T>C; NM_001271208.2:c.21522+3A>G) in NEB. Transcriptomic sequencing on affected individual muscles revealed that the extended splice variant c.21522+3A>G causes exon 144 skipping. Nebulin isoforms containing exon 144 are known to be mutually exclusive with isoforms containing exon 143, and these isoforms are differentially expressed during development and in adult skeletal muscles. Affected individuals' MRI patterns of muscle involvement were compared with the known pattern of relative abundance of these two isoforms in muscle. We propose that the pattern of muscle involvement in these affected individuals better fits the distribution of exon 144-containing isoforms in muscle than with previously published MRI findings in NEB-related disease due to other variants. Our report introduces disease pathogenesis and manifestation as a result of alteration of isoform distributions in muscle., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)
Published: 2025
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27. Novel AIRTrode-based wearable electrode supports long-term, online brain-computer interface operations.

Author: H Liu D, Hsieh JC, Alawieh H, Kumar S, Iwane F, Pyatnitskiy I, Ahmad ZJ, Wang H, and Millán JDR
Subjects: Humans, Male, Adult, Female, Young Adult, Online Systems, Brain-Computer Interfaces, Electroencephalography methods, Electroencephalography instrumentation, Electrodes, Wearable Electronic Devices
Abstract: Objective. Non-invasive electroencephalograms (EEG)-based brain-computer interfaces (BCIs) play a crucial role in a diverse range of applications, including motor rehabilitation, assistive and communication technologies, holding potential promise to benefit users across various clinical spectrums. Effective integration of these applications into daily life requires systems that provide stable and reliable BCI control for extended periods. Our prior research introduced the AIRTrode, a self-adhesive (A), injectable (I), and room-temperature (RT) spontaneously-crosslinked hydrogel electrode (AIRTrode). The AIRTrode has shown lower skin-contact impedance and greater stability than dry electrodes and, unlike wet gel electrodes, does not dry out after just a few hours, enhancing its suitability for long-term application. This study aims to demonstrate the efficacy of AIRTrodes in facilitating reliable, stable and long-term online EEG-based BCI operations. Approach. In this study, four healthy participants utilized AIRTrodes in two BCI control tasks-continuous and discrete-across two sessions separated by six hours. Throughout this duration, the AIRTrodes remained attached to the participants' heads. In the continuous task, participants controlled the BCI through decoding of upper-limb motor imagery (MI). In the discrete task, the control was based on decoding of error-related potentials (ErrPs). Main Results. Using AIRTrodes, participants demonstrated consistently reliable online BCI performance across both sessions and tasks. The physiological signals captured during MI and ErrPs tasks were valid and remained stable over sessions. Lastly, both the BCI performances and physiological signals captured were comparable with those from freshly applied, research-grade wet gel electrodes, the latter requiring inconvenient re-application at the start of the second session. Significance. AIRTrodes show great potential promise for integrating non-invasive BCIs into everyday settings due to their ability to support consistent BCI performances over extended periods. This technology could significantly enhance the usability of BCIs in real-world applications, facilitating continuous, all-day functionality that was previously challenging with existing electrode technologies., (Creative Commons Attribution license.)
Published: 2025
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28. Electrically Active Biomaterials for Stimulation and Regeneration in Tissue Engineering.

Author: Park J, Akbaba GE, Sharma N, Das R, Vinikoor T, Liu Y, Le DQ, Angadi K, and Nguyen TD
Subjects: Humans, Animals, Electric Stimulation, Regeneration, Tissue Engineering methods, Biocompatible Materials chemistry
Abstract: In the human body, bioelectric cues are crucial for tissue stimulation and regeneration. Electrical stimulation (ES) significantly enhances the regeneration of nerves, bones, cardiovascular tissues, and wounds. However, the use of conventional devices with stimulating metal electrodes is invasive and requires external batteries. Consequently, electrically active materials with excellent biocompatibility have attracted attention for their applications in stimulation and regeneration in tissue engineering. To fully exploit the potential of these materials, biocompatibility, operating mechanisms, electrical properties, and even biodegradability should be carefully considered. In this review, we categorize various electrically active biomaterials based on their mechanisms for generating electrical cues, such as piezoelectric effect, triboelectric effect, and others. We also summarize the key material properties, including electrical characteristics and biodegradability, and describe their applications in tissue stimulation and regeneration for nerves, musculoskeletal tissues, and cardiovascular tissues. The electrically active biomaterials hold great potential for advancing the field of tissue engineering and their demonstrated success underscores the importance of continued research in this field., (© 2025 Wiley Periodicals LLC.)
Published: 2025
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29. Single and two-dose typhoid conjugate vaccine safety and immunogenicity in HIV-exposed uninfected and HIV-unexposed uninfected Malawian children.

Author: Nampota-Nkomba N, Nyirenda OM, Mapemba V, Masonga R, Patel PD, Misiri T, Mwakiseghile F, Wachepa R, Ndaferankhande JM, Lipenga B, Patel P, Banda H, Oshinsky J, Pasetti MF, Heyderman RS, Jamka LP, Hosangadi D, Datta S, Gordon MA, Neuzil KM, and Laurens MB
Subjects: Humans, Male, Female, Malawi, Infant, Immunoglobulin G blood, Tetanus Toxoid immunology, Tetanus Toxoid adverse effects, Tetanus Toxoid administration & dosage, Immunization Schedule, Vaccination, HIV Infections immunology, Typhoid-Paratyphoid Vaccines immunology, Typhoid-Paratyphoid Vaccines adverse effects, Typhoid-Paratyphoid Vaccines administration & dosage, Vaccines, Conjugate immunology, Vaccines, Conjugate adverse effects, Vaccines, Conjugate administration & dosage, Antibodies, Bacterial blood, Typhoid Fever immunology, Typhoid Fever prevention & control, Immunogenicity, Vaccine
Abstract: Vaccine safety and immunogenicity data in human immunodeficiency virus (HIV)-exposed uninfected (HEU) children are important for decision-making in HIV and typhoid co-endemic countries. In an open-label study, we recruited Malawian HEU and HIV unexposed uninfected (HUU) infants aged 9 - 11 months. HEU participants were randomized to receive Vi-tetanus toxoid conjugate vaccine (Vi-TT) at 9 months, Vi-TT at 15 months, or Vi-TT at 9 and 15 months. HUU participants received Vi-TT at 9 and 15 months. Safety outcomes included solicited and unsolicited adverse events (AE) and serious AEs (SAEs) within 7 days, 28 days, and 6 months of vaccination, respectively. Serum was collected before and at day 28 after each vaccination to measure anti-Vi IgG antibodies by enzyme-linked immunosorbent assay (ELISA). Cohort 1 (66 participants) enrollment began 02 December 2019, and follow-up was terminated before completion due to the COVID-19 pandemic. Cohort 2 (100 participants) enrollment began 25 March 2020. Solicited AEs were mostly mild, with no significant differences between HEU and HUU participants or one- and two-dose groups. All six SAEs were unrelated to vaccination. Anti-Vi geometric mean titers (GMT) increased significantly from 4.1 to 4.6 ELISA units (EU)/mL at baseline to 2572.0 - 4117.6 EU/mL on day 28 post-vaccination, and similarly between HEU and HUU participants for both one- and two-dose schedules. All participants seroconverted (>4-fold increase in GMT) by the final study visit. Our findings of comparable safety and immunogenicity of Vi-TT in HUU and HEU children support country introductions with single-dose Vi-TT in HIV-endemic countries.
Published: 2024
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30. Advancing Drug Development in Myelodysplastic Syndromes.

Author: Mina A, McGraw KL, Cunningham L, Kim N, Jen EY, Calvo KR, Ehrlich LA, Aplan PD, Garcia-Manero G, Foran JM, Garcia JS, Zeidan AM, DeZern AE, Komrokji RS, Sekeres MA, Scott BL, Buckstein RJ, Tinsley-Vance S, Verma A, Wroblewski T, Pavletic SZ, and Norsworthy KJ
Abstract: Myelodysplastic syndromes/neoplasms (MDS) are heterogeneous stem cell malignancies characterized by poor prognosis and no curative therapies outside of allogeneic hematopoietic stem cell transplantation. Despite some recent approvals by the United States Food and Drug Administration (FDA), (e.g., luspatercept, ivosidenib, decitabine/cedazuridine and imetelstat), there has been little progress in the development of truly transformative therapies for the treatment of patients with MDS. Challenges to advancing drug development in MDS are multifold but may be grouped into specific categories including criteria for risk stratification and eligibility, response definitions, time-to-event endpoints, transfusion endpoints, functional assessments, and biomarker development. Strategies to address these challenges and optimize future clinical trial design for patients with MDS are presented here., (Copyright © 2024 American Society of Hematology.)
Published: 2024
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31. Human iPSC-based disease modeling studies identify a common mechanistic defect and potential therapies for AMD and related macular dystrophies.

Author: Dalvi S, Roll M, Chatterjee A, Kumar LK, Bhogavalli A, Foley N, Arduino C, Spencer W, Reuben-Thomas C, Ortolan D, Pébay A, Bharti K, Anand-Apte B, and Singh R
Subjects: Humans, Retinal Drusen metabolism, Retinal Drusen pathology, Receptor for Advanced Glycation End Products metabolism, Models, Biological, Male, Aged, Induced Pluripotent Stem Cells metabolism, Induced Pluripotent Stem Cells pathology, Macular Degeneration metabolism, Macular Degeneration pathology, Retinal Pigment Epithelium metabolism, Retinal Pigment Epithelium pathology, Matrix Metalloproteinase 2 metabolism
Abstract: Age-related macular degeneration (AMD) and related macular dystrophies (MDs) primarily affect the retinal pigment epithelium (RPE) in the eye. A hallmark of AMD/MDs that drives later-stage pathologies is drusen. Drusen are sub-RPE lipid-protein-rich extracellular deposits, but how drusen forms and accumulates is not known. We utilized human induced pluripotent stem cell (iPSC)-derived RPE from patients with AMD and three distinct MDs to demonstrate that reduced activity of RPE-secreted matrix metalloproteinase 2 (MMP2) contributes to drusen in multiple maculopathies in a genotype-agnostic manner by instigating sterile inflammation and impaired lipid homeostasis via damage-associated molecular pattern molecule (DAMP)-mediated activation of receptor for advanced glycation end-products (RAGE) and increased secretory phospholipase 2-IIA (sPLA2-IIA) levels. Therapeutically, RPE-specific MMP2 supplementation, RAGE-antagonistic peptide, and a small molecule inhibitor of sPLA2-IIA ameliorated drusen accumulation in AMD/MD iPSC-RPE. Ultimately, this study defines a causal role of the MMP2-DAMP-RAGE-sPLA2-IIA axis in AMD/MDs., Competing Interests: Declaration of interests University of Rochester has filed a provisional US patent application: U.S. Provisional Patent Application No. 63/632,123, filed April 10, 2024, title: “Drug Treatment for Macular Degeneration.”, (Published by Elsevier Inc.)
Published: 2024
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32. Interleukin-13 Receptor Subunit Alpha 2 Induces Chemokine Expression and Macrophage Polarization to Promote Inflammation and Fibrosis.

Author: Kwon S, Chung EJ, Kc S, White AO, Chung SI, Horton JA, Yun HS, Ahn H, Shankavaram U, Chung JY, Song JS, and Citrin DE
Abstract: Purpose: Interleukin-13 (IL-13) is a known mediator of radiation-induced lung injury (RILI). IL-13Rα2 has an accepted role in antagonizing IL-13 signaling by acting as a decoy receptor. We sought to understand the role of IL-13Rα2 in the progression of RILI., Methods and Materials: Mice deficient in IL-13Rα2 (Ra2 KO) and wild-type (WT) mice were exposed to thoracic irradiation (IR) in 5 daily fractions of 6 Gy and followed for survival (n > 15 per group) and tissue collection (n > 5 per group). Collagen accumulation in the lung was evaluated with Masson's trichrome staining and hydroxyproline content. Gene expression was evaluated by RNA sequencing. Expression of IL-13Rα2 and macrophage markers in murine lung and human lung tissue (n = 63) was assessed with immunohistochemistry. The role of IL-13Rα2 in IL-13-mediated macrophage polarization was determined in primary macrophage cultures from Ra2 KO mice and after RNA silencing of a human monocyte cell line (THP-1)., Results: Membrane-bound IL-13Rα2 expression in murine lung was increased after IR and localized to macrophages. Irradiated Ra2 KO mice exhibited reduced sensitivity to thoracic IR compared with WT mice as measured by median survival (19 vs. 21 weeks, P < .05), histology, hydroxyproline content, transforming growth factor-β expression, and macrophage accumulation. Gene sets linked to cytokine signaling and macrophage recruitment were enriched in irradiated WT compared with Ra2 KO lung tissue. IL-13-mediated expression of CCL2 and M2 markers was reduced in murine and human macrophages deficient in IL-13Rα2. Increased expression of in IL-13Rα2 and co-localization with CD163 was confirmed in irradiated fibrotic human lung., Conclusions: IL-13Rα2 is predominantly expressed in macrophages within irradiated lung and plays a crucial role in CCL2 expression, macrophage polarization, and transforming growth factor-β expression in response to IL-13. These studies demonstrate an unexpected profibrotic role of IL-13Rα2 in RILI and suggest that strategies targeting IL-13Rα2 may ameliorate chronic inflammation and fibrosis., (Published by Elsevier Inc.)
Published: 2024
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33. Evaluation of dimethandrolone undecanoate in non-human primates as a candidate for long-acting injectable male contraceptive.

Author: Bunin DI, Kim K, Parman T, Gahagen J, Zelinski MB, Adevai T, Wang C, Tang L, Iyer L, Endsley A, Blithe DL, and Lee MS
Abstract: Background: Dimethandrolone undecanoate (DMAU) is under development as a single agent hormonal male contraceptive. DMAU is a prodrug hydrolyzed by esterase(s) to the active metabolite dimethandrolone (DMA) which has dual androgenic and progestogenic actions. Phase 1 clinical trial results show DMAU to be well-tolerated as an oral contraceptive in healthy men; however, delivery of DMAU as a long-acting injectable rather than a daily oral formulation would provide user compliance benefits and address oral bioavailability concerns., Objective: To assess the safety, pharmacokinetics (PK), and long-acting contraceptive potential of DMAU in male non-human primates (NHP) when delivered as an injectable or oral formulation., Materials and Methods: DMAU was administered to cynomolgus macaques orally for 9 months or as five weekly intramuscular (IM) injections and to rhesus macaques as a single IM injection. Evaluations of safety, fertility indicators, and serum levels of DMAU and DMA were followed > 2 years post-dose., Results: Repeat dose oral and IM administrations were well-tolerated with no significant toxicological findings. Dramatic reductions in serum testosterone concentration occurred within days of administration followed by sustained suppression of additional fertility indicators (e.g., serum inhibin B, sperm count, and testicular spermatogenesis). Slight body weight increases and reductions in testes weight also occurred. Repeat DMAU injections resulted in DMA serum concentrations above the lower limit of quantification (1 ng/mL) for > 500 days. DMAU PK parameters increased with increasing IM dose, while dose dependence was not seen for serum DMA concentrations suggesting a depot effect with a reservoir of non-circulating prodrug remaining at the injection site which gets slowly hydrolyzed to DMA and absorbed into circulation. Testosterone levels and spermatogenesis returned by the end of the recovery period., Conclusions: Nonclinical safety, PK, and pharmacodynamic data in male NHP demonstrate the safe, well-tolerated, long-acting, and reversible contraceptive potential of injectable DMAU., (© 2024 The Author(s). Andrology published by John Wiley & Sons Ltd on behalf of American Society of Andrology and European Academy of Andrology.)
Published: 2024
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34. Evaluation of face validity and core concepts of a novel knowledge scale for inherited heart disease: A pilot study.

Author: Christian S, Dzwiniel T, Baker A, Biesecker B, Borle K, Mostafavi R, Slamon J, Wand H, and Yeates L
Abstract: The rising demand for genetic counseling has prompted the implementation of various innovative service delivery models, such as patient webinars, videos, chatbots, and the integration of genetic testing into mainstream healthcare. To ensure patients receive adequate information for informed decision-making, validated measures to assess these models are essential but currently limited in the setting of inherited heart disease. We aimed to develop and initiate validation of a cardiac knowledge scale, as part of the Multidimensional Model of Informed Choice measure, to assess whether patients (probands and family members) with inherited cardiomyopathies, arrhythmias, and aortopathies are provided with sufficient knowledge to make informed decisions about genetic testing. Content expert genetic counselors identified eight core concepts addressed during genetic counseling sessions; from these, eight true/false knowledge questions were created. Questions were reviewed by 22 international cardiac genetics counselors with additional changes made. Initial validation steps of the knowledge scale were conducted at two sites: the Edmonton Medical Genetic Clinic, University of Alberta Hospital in Edmonton, Canada, and the Genetic Heart Disease Clinic, Royal Prince Alfred Hospital in Sydney, Australia. Face validity was evaluated through nine patient interviews, resulting in minor revisions to four questions and major revisions to one question. An additional five patient interviews were conducted to evaluate the revised questions. The core concepts addressed in each question were further evaluated in the context of patient decision-making about genetic testing. All participants described the eight concepts as either helpful or essential in their decision-making process. The cardiac knowledge scale is a promising measure created to evaluate the informed choice of patients and their families affected by an inherited heart condition. The next step of validation includes trialing the cardiac knowledge scale with a real-world sample of patients deciding about genetic testing for inherited heart disease., (© 2024 The Author(s). Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)
Published: 2024
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35. Factors impacting time to genetic diagnosis for children with epilepsy.

Author: Rimmasch M, Wilson CA, Walton NA, Huynh K, Bonkowsky JL, and Palmquist R
Subjects: Humans, Male, Female, Child, Retrospective Studies, Child, Preschool, Adolescent, Developmental Disabilities genetics, Developmental Disabilities diagnosis, Delayed Diagnosis, Time Factors, Infant, Hospitalization, Epilepsy genetics, Epilepsy diagnosis, Genetic Testing
Abstract: Molecular diagnosis for pediatric epilepsy patients can impact treatment and health supervision recommendations. However, there is little known about factors affecting the time to receive a diagnosis. Our objective was to characterize factors affecting the time from first seizure to molecular diagnosis in children with epilepsy. A retrospective, population-based review was used to analyze data from pediatric patients with a genetic etiology for epilepsy over a 5 year period. A subgroup of patients with seizure onset after 2016 was evaluated for recent trends. We identified 119 patients in the main cohort and 62 in a more recent (contemporaneous) subgroup. Sex, race, and ethnicity were not significantly associated with time to molecular diagnosis. A greater number of hospitalizations was associated with a shorter time to diagnosis (p < 0.001). Developmental delay was associated with a longer time to diagnosis (p = 0.002). We found no association for time to diagnosis with a diagnosis of autism, utilization of free genetic testing, or epilepsy type. In the recent subgroup analysis, commercial insurance was associated with decreased time to diagnosis (p = 0.02). Developmental delay, public insurance, or patients in the outpatient setting had longer times to molecular diagnosis. These findings suggest that there may be opportunities to implement interventions aimed at accelerating the provision of genetic testing in pediatric epilepsy. PLAIN LANGUAGE SUMMARY: Genetic diagnosis for pediatric epilepsy patients can impact treatment and care. This study looked at factors that affect how long it takes a pediatric epilepsy patient to receive a genetic diagnosis. We found that sex, race and ethnicity, epilepsy type, and whether the patient had autism did not affect how long it took the patient to receive a diagnosis. However, we found that patients with developmental delay, fewer hospitalizations, and public insurance took a longer time to receive a diagnosis. Our findings suggest potential strategies for reducing the time to receive a genetic diagnosis., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Published: 2024
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36. A Call to Arms: Overcoming challenges in Myelodysplastic Syndromes therapy advances.

Author: McGraw KL, Aplan PD, and Pavletic SZ
Published: 2024
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37. Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1/2a trial.

Author: Julg B, Walker-Sperling VEK, Wagh K, Aid M, Stephenson KE, Zash R, Liu J, Nkolola JP, Hoyt A, Castro M, Serebryannyy L, Yanosick K, Speidel T, Borducchi EN, Murzda T, Maxfield L, Arduino R, McDermott AB, Gama L, Giorgi EE, Koup RA, Seaman MS, Rolle CP, DeJesus E, Li W, Korber B, and Barouch DH
Subjects: Humans, Male, Adult, Female, Middle Aged, Broadly Neutralizing Antibodies immunology, Broadly Neutralizing Antibodies therapeutic use, CD4 Lymphocyte Count, Viral Load drug effects, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal immunology, HIV-1 immunology, HIV-1 drug effects, HIV Infections drug therapy, HIV Infections immunology, HIV Infections virology, HIV Antibodies immunology, Antibodies, Neutralizing immunology
Abstract: Human immunodeficiency virus type 1 (HIV-1)-specific broadly neutralizing monoclonal antibodies (bNAbs) have to date shown transient viral suppression when administered as monotherapy or as a cocktail of two antibodies 1-4 . A combination of three bNAbs provides improved neutralization coverage of global viruses, which may more potently suppress viral escape and rebound 5-7 . Here we performed an open-label, two-part study evaluating a single intravenous dose of HIV-1 bNAbs, PGT121, PGDM1400 and VRC07-523LS, in six adults without HIV in part 1 and a multicenter trial of up to six monthly infusions of these three bNAbs in 12 people living with HIV with an antiretroviral therapy (ART) interruption in part 2. The primary endpoints were safety, tolerability and pharmacokinetics, and the secondary endpoints in part 2 were antiviral activity following ART discontinuation, changes in CD4 + T cell counts and development of HIV-1 sequence mutations associated with bNAb resistance. The trial met its prespecified endpoints. The bNAb treatment was generally safe and well tolerated. In part 2, 83% of participants (10 of 12) maintained virologic suppression for the duration of antibody therapy for at least 28 weeks, and 42% of participants (5 of 12) showed virologic suppression for at least 38-44 weeks, despite the decline of serum bNAb concentrations to low or undetectable levels. In exploratory analyses, early viral rebound in two individuals correlated with baseline resistance to PGT121 and PGDM1400, whereas long-term virologic control in five individuals correlated with reduced immune activation, T cell exhaustion and proinflammatory signaling following bNAb therapy. Our data show the potential of a triple bNAb cocktail to suppress HIV-1 in the absence of ART. ClinicalTrials.gov registration: NCT03721510 ., Competing Interests: Competing interests: B.J. is a part-time employee of Leyden Labs, B.V. The other authors declare no competing interests., (© 2024. The Author(s).)
Published: 2024
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38. Enzyme applications in baking: From dough development to shelf-life extension.

Author: Chowdhury MAH, Sarkar F, Reem CSA, Rahman SM, Mahamud AGMSU, Rahman MA, and Md Ashrafudoulla
Subjects: Enzymes chemistry, Enzymes metabolism, Flour, Bread, Rheology, Fermentation, Cooking
Abstract: Enzymes play a vital role in baking, providing significant benefits from dough development to extending shelf life, which enhances product quality and consistency. Acting as biological catalysts, enzymes such as proteases and amylases break down proteins and starches, modifying dough rheology and improving fermentation. Lipases and oxidases further refine dough texture through emulsification and oxidation, while lipases also produce fatty acid derivatives during fermentation, contributing to the flavor and aroma of baked goods. Xylanases and cellulases optimize dough handling by altering fiber structure, and amylases help maintain moisture and texture, extending the shelf life of baked products. Ensuring regulatory compliance is essential when incorporating enzymes into baking processes, as bakers must address enzyme stability and determine appropriate dosages for reliable outcomes. Ongoing research is exploring innovative enzyme applications, including customized enzyme blends that target specific product qualities, offering new possibilities for product differentiation and innovation. In summary, enzyme-driven advancements present bakers with opportunities to improve product quality, shelf life, and consistency, while meeting industry regulations. This review emphasizes the critical impact enzymes have on dough properties and finished product characteristics, highlighting their role in driving future innovations within the baking industry., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Published by Elsevier B.V.)
Published: 2024
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39. Cortisol and ACTH response to Dex/CRH testing and 24-hour urine free cortisol levels in women with and without premenstrual dysphoric disorder.

Author: Zou CX, Guerrieri GM, Martinez PE, Li X, Ben Dor R, Bovell RTM, Naredo Rojas JM, McCluggage P, Kress N, Neiman LK, Rubinow DR, and Schmidt PJ
Abstract: Hyperactive and hyperreactive HPA axis functions are frequently reported in depressive disorders, particularly in major depression. However, research into HPA axis function in women with premenstrual dysphoric disorder (PMDD), which is also classified as a depressive disorder, has shown inconsistent results. This study aimed to characterize the HPA axis in women with PMDD using the combined dexamethasone suppression and CRH stimulation (Dex/CRH) test, alongside measurements of 24-hour urine free cortisol (UFC). We enrolled 26 women with prospectively confirmed PMDD and 25 asymptomatic controls (ACs), testing them during the mid-follicular and luteal phases of the menstrual cycle. The primary outcomes included serial plasma cortisol and ACTH levels, their area-under-the-curve (AUC), and 24-hour UFC levels. We utilized a mixed model to compare serial cortisol and ACTH levels, and the Wilcoxon Signed Rank test for comparing UFC levels and cortisol and ACTH AUC. No significant effects related to diagnosis or menstrual cycle phase were observed on plasma cortisol or ACTH levels (from time 0 to +75 minutes), nor on the AUCs of plasma cortisol or ACTH (p > 0.05 for all comparisons). Notably, the PMDD group displayed significantly lower 24-hour UFC levels compared to the AC group during both the follicular and luteal phases (p = 0.0004 and p = 0.0007, respectively). The observed hyposecretion of cortisol in the PMDD group suggests a pathophysiology distinct from other depressive disorders, possibly aligning more closely with stress disorders such as PTSD. The unique symptom profile of PMDD, marked by significant irritability and a more rapid response to antidepressant treatment than is typical in major depression, further supports considering an alternative classification., Competing Interests: Declaration of Competing Interest None. Disclosure statement This work was written as part of Constance Zou’s official duties as a government employee. The views expressed in this article do not necessarily represent the views of the NIMH, NIH, HHS, or the United States Government. None of the other Authors have any disclosures to report., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
Published: 2024
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40. Multi-ancestry genome-wide association study reveals novel genetic signals for lung function decline.

Author: Patchen BK, Zhang J, Gaddis N, Bartz TM, Chen J, Debban C, Leonard H, Nguyen NQ, Seo J, Tern C, Allen R, DeMeo DL, Fornage M, Melbourne C, Minto M, Moll M, O'Connor G, Pottinger T, Psaty BM, Rich SS, Rotter JI, Silverman EK, Stratford J, Graham Barr R, Cho MH, Gharib SA, Manichaikul A, North K, Oelsner EC, Simonsick EM, Tobin MD, Yu B, Choi SH, Dupuis J, Cassano PA, and Hancock DB
Abstract: Rationale: Accelerated decline in lung function contributes to the development of chronic respiratory disease. Despite evidence for a genetic component, few genetic associations with lung function decline have been identified., Objectives: To evaluate genome-wide associations and putative downstream functionality of genetic variants with lung function decline in diverse general population cohorts., Methods: We conducted genome-wide association study (GWAS) analyses of decline in the forced expiratory volume in the first second (FEV 1 ), forced vital capacity (FVC), and their ratio (FEV 1 /FVC) in participants across six cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. Genotypes were imputed to TOPMed (CHARGE cohorts) or Haplotype Reference Consortium (HRC) (UK Biobank) reference panels, and GWAS analyses used generalized estimating equation models with robust standard error. Models were stratified by cohort, ancestry, and sex, and adjusted for important lung function confounders and genotype principal components. Results were combined in cross-ancestry and ancestry-specific meta-analyses. Selected top variants were tested for replication in two independent COPD-enriched cohorts., Measurements and Main Results: Our discovery analyses included 52,056 self-reported White (N=44,988), Black (N=5,788), Hispanic (N=550), and Chinese American (N=730) participants with a mean of 2.3 spirometry measurements and 8.6 years of follow-up. Functional mapping of GWAS meta-analysis results identified 361 distinct genome-wide significant (p<5E-08) variants in one or more of the FEV 1 , FVC, and FEV 1 /FVC decline phenotypes, which overlapped with previously reported genetic signals for several related pulmonary traits. Of these, 8 variants, or 20.5% of the variant set available for replication testing, were nominally associated (p<0.05) with at least one decline phenotype in COPD-enriched cohorts (White [N=4,778] and Black [N=1,118]). Using the GWAS results, gene-level analysis implicated 38 genes, including eight ( XIRP2 , GRIN2D , SATB1 , MARCHF4 , SIPA1L2 , ANO5 , H2BC10 , and FAF2 ) with consistent associations across ancestries or decline phenotypes. Annotation class analysis revealed significant enrichment of several regulatory processes for corticosteroid biosynthesis and metabolism. Drug repurposing analysis identified 43 approved compounds targeting eight of the implicated 38 genes., Conclusions: Our multi-ancestry GWAS meta-analyses identified numerous genetic loci associated with lung function decline. These findings contribute knowledge to the genetic architecture of lung function decline, provide evidence for a role of endogenous corticosteroids in the etiology of lung function decline, and identify drug targets that merit further study for potential repurposing to slow lung function decline and treat lung disease., Competing Interests: COMPETING INTERESTS BMP serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. No other others have competing interests to declare.
Published: 2024
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41. Bladder image stitching algorithm for navigation and referencing using a standard cystoscope.

Author: Li M, Varble NA, Gurram S, Long D, Valera V, Gopal N, Bakhutashvili I, Reed S, Pritchard WF, Karanian JW, Xu S, and Wood BJ
Subjects: Animals, Swine, Urinary Bladder Neoplasms diagnostic imaging, Urinary Bladder Neoplasms pathology, Cystoscopes, Image Processing, Computer-Assisted methods, Humans, Algorithms, Urinary Bladder diagnostic imaging, Cystoscopy methods, Phantoms, Imaging
Abstract: To aid in the diagnosis, monitoring, and surveillance of bladder carcinoma, this study aimed to develop and test an algorithm that creates a referenceable bladder map rendered from standard cystoscopy videos without the need for specialized equipment. A vision-based algorithm was developed to generate 2D bladder maps from individual video frames, by sequentially stitching image frames based on matching surface features, and subsequently localize and track frames during reevaluation. The algorithm was developed and calibrated in a 2D model and 3D anthropomorphic bladder phantom. The performance was evaluated in vivo in swine and with retrospective clinical cystoscopy video. Results showed that the algorithm was capable of capturing and stitching intravesical images with different sweeping patterns. Between 93% and 99% of frames had sufficient features for bladder map generation. Upon reevaluation, the cystoscope accurately localized a frame within 4.5 s. In swine, a virtual mucosal surface map was generated that matched the explant anatomy. A surface map could be generated based on archived patient cystoscopy images. This tool could aid recording and referencing pathologic findings and biopsy or treatment locations for subsequent procedures and may have utility in patients with metachronous bladder cancer and in low-resource settings., Competing Interests: Declarations. Competing interests: NV is an employee of Philips. BJW is the Principal Investigator in Cooperative Research and Development Agreements between NIH and the following: BTG Biocompatibles/Boston Scientific, Siemens, NVIDIA, Celsion Corp, Canon Medical, XAct Robotics, and Philips. BJW and NIH are party to Material Transfer or Collaboration Agreements with: Angiodynamics, 3T Technologies, Profound Medical, Exact Imaging, Johnson and Johnson, Endocare/Healthtronics, and Medtronic. Outside the submitted work, BJW is primary inventor on 47 issued patents owned by the NIH (list available upon request), a portion of which have been licensed by NIH to Philips. BJW and NIH report a licensing agreement with Canon Medical on algorithm software with no patent. BJW is joint inventor (assigned to HHS NIH US Government (for patents and pending patents related to drug eluting bead technology, some of which may have joint inventorships with BTG Biocompatibles/Boston Scientific. BJW is primary inventor on patents owned by NIH in the space of drug eluting embolic beads. No other authors have conflicts of interest to declare., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Published: 2024
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42. Characterization of Somatostatin Receptor 2 Gene Expression and Immune Landscape in Sinonasal Malignancies.

Author: Xue E, Bracken-Clarke D, Krause H, Adeyelu T, Evans MG, Akbulut D, Quezado M, Gandhi N, Farrell A, Soares HP, Lou E, Phan M, Patel R, Vanderwalde AM, Elliott A, Steuer CE, Saba NF, Lubin DJ, London NR Jr, Gulley JL, and Floudas CS
Abstract: Olfactory neuroblastoma (ONB), sinonasal undifferentiated carcinoma (SNUC), and sinonasal neuroendocrine carcinoma (SNEC) are rare malignancies arising from the sinonasal tract with limited therapeutic options. The expression of the somatostatin receptor 2 gene ( SSTR2 ), which is expressed in other neuroendocrine neoplasms and is therapeutically actionable, has been reported in these tumors. Here, we analyzed SSTR2 gene expression and its associations with genomic features, established biomarkers predicting of immune response, and the tumor immune microenvironment in a cohort of ONB, SNUC, and SNEC tumor samples (26, 13, and 8 samples, respectively) from a real-world database. SSTR2 gene expression was high in neural-type ONB and low in basal-type ONB and in most of the SNUC and SNEC cases; there was no difference in expression between primary and metastatic tumors. The T cell-inflamed (TCI) score analysis classified 38.5% of SNUC cases as T cell-inflamed compared to only 3.9% of ONB and 0% of SNEC cases; 26.9% of ONB cases were classified as intermediate TCI; and SNEC had the lowest relative immune cell infiltration by deconvolution. In high SSTR2 -expressing ONB, there was a higher proportion of infiltrating of Natural Killer cells and dendritic cells by deconvolution. Additionally, high SSTR2 -expressing ONB was enriched for proliferation pathways, including E2F and Myc targets and G2M checkpoints. In conclusion, our findings delineate significant differences between these three types of sinonasal malignancies that were examined. In ONB, relative to SNUC and SNEC, the SSTR2 expression profile, combined with its immune profiles, indicates potential novel therapeutic strategies and combinations for this unmet clinical need. Conversely, the inflammatory microenvironment of SNUC may be targetable using immuno-oncologic therapies.
Published: 2024
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43. A Natural History Study of Timothy Syndrome.

Author: Timothy KW, Bauer R, Larkin KA, Walsh EP, Abrams DJ, Gonzalez Corcia C, Valsamakis A, Pitt GS, Dick IE, and Golden A
Subjects: Humans, Female, Male, Autistic Disorder genetics, Phenotype, Child, Genotype, Infant, Child, Preschool, Mutation genetics, Adolescent, Long QT Syndrome genetics, Syndactyly genetics, Calcium Channels, L-Type genetics
Abstract: Background: Timothy syndrome (OMIM #601005) is a rare disease caused by variants in the gene CACNA1C. Initially, Timothy syndrome was characterized by a cardiac presentation of long QT syndrome and syndactyly of the fingers and/or toes, all associated with the CACNA1C variant, Gly406Arg. However, subsequent identification of diverse variants in CACNA1C has expanded the clinical spectrum, revealing various cardiac and extra-cardiac manifestations. It remains underexplored whether individuals with the canonical Gly406Arg variants in mutually exclusive exon 8A (Timothy syndrome 1) or exon 8 (Timothy syndrome 2) exhibit overlapping symptoms. Moreover, case reports have indicated that some CACNA1C variants may produce a cardiac-selective form of Timothy syndrome often referred to as non-syndromic long QT type 8 or cardiac-only Timothy syndrome, however few reports follow up on these patients to confirm the cardiac selectivity of the phenotype over time., Methods: A survey was administered to the parents of patients with Timothy syndrome, querying a broad range of symptoms and clinical features. Study participants were organized into 5 separate categories based on genotype and initial diagnosis, enabling comparison between groups of patients which have been described differentially in the literature., Results: Our findings reveal that Timothy syndrome patients commonly exhibit both cardiac and extra-cardiac features, with long QT syndrome, neurodevelopmental impairments, hypoglycemia, and respiratory issues being frequently reported. Notably, the incidence of these features was similar across all patient categories, including those diagnosed with non-syndromic long QT type 8, suggesting that the 'non-syndromic' classification may be incomplete., Conclusions: This study represents the first Natural History Study of Timothy syndrome, offering a comprehensive overview of the disease's clinical manifestations. We demonstrate that both cardiac and extra-cardiac features are prevalent across all patient groups, underscoring the syndromic nature of CACNA1C variants. While the critical role of long QT syndrome and cardiac arrhythmias in Timothy syndrome has been well recognized, our findings indicate that hypoglycemia and respiratory dysfunction also pose significant life-threatening risks, emphasizing the need for comprehensive therapeutic management of affected individuals., Competing Interests: Declarations. Ethics approval and consent to participate: Data within this study was collected after informed consent from the TS individual or parent/guardian completing the survey on their behalf. The study was approved by the Institutional Review Board of Genetic Alliance (Washington, DC, USA). Consent for publication: All participants provided consent consistent with the IRB approved by Genetic Alliance. Competing interests: The authors have no competing financial interests., (© 2024. The Author(s).)
Published: 2024
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44. Patch-walking, a coordinated multi-pipette patch clamp for efficiently finding synaptic connections.

Author: Yip MC, Gonzalez MM, Lewallen CF, Landry CR, Kolb I, Yang B, Stoy WM, Fong MF, Rowan MJM, Boyden ES, and Forest CR
Subjects: Animals, Mice, Brain physiology, Brain cytology, Male, Patch-Clamp Techniques methods, Synapses physiology, Neurons physiology
Abstract: Significant technical challenges exist when measuring synaptic connections between neurons in living brain tissue. The patch clamping technique, when used to probe for synaptic connections, is manually laborious and time-consuming. To improve its efficiency, we pursued another approach: instead of retracting all patch clamping electrodes after each recording attempt, we cleaned just one of them and reused it to obtain another recording while maintaining the others. With one new patch clamp recording attempt, many new connections can be probed. By placing one pipette in front of the others in this way, one can 'walk' across the mouse brain slice, termed 'patch-walking.' We performed 136 patch clamp attempts for two pipettes, achieving 71 successful whole cell recordings (52.2%). Of these, we probed 29 pairs (i.e. 58 bidirectional probed connections) averaging 91 μm intersomatic distance, finding three connections. Patch-walking yields 80-92% more probed connections, for experiments with 10-100 cells than the traditional synaptic connection searching method., Competing Interests: MY, MG, CL, CL, BY, MF, EB No competing interests declared, IK IK., WMS, and CRF are co-inventors on a patent (US10830758B2) describing pipette cleaning that is licensed by Sensapex, WS, CF IK, WMS, and CRF are co-inventors on a patent (US10830758B2) describing pipette cleaning that is licensed by Sensapex, MR Reviewing editor, eLife
Published: 2024
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45. Chronic Viral Reactivation and Associated Host Immune Response and Clinical Outcomes in Acute COVID-19 and Post-Acute Sequelae of COVID-19.

Author: Maguire C, Chen J, Rouphael N, Pickering H, Phan HV, Glascock A, Chu V, Dandekar R, Corry D, Kheradmand F, Baden LR, Selaky R, McComsey GA, Haddad EK, Cairns CB, Pulendran B, Fernandez-Sesma A, Simon V, Metcalf JP, Higuita NIA, Messer WB, David MM, Nadeau KC, Kraft M, Bime C, Schaenman J, Erle D, Calfee CS, Atkinson MA, Brackenridge SC, Ehrlich LIR, Montgomery RR, Shaw AC, Hough CL, Geng LN, Hafler DA, Augustine AD, Becker PM, Peters B, Ozonoff A, Kim-Schulze SH, Krammer F, Bosinger S, Eckalbar W, Altman MC, Wilson M, Guan L, Kleinstein SH, Smolen KK, Reed EF, Levy O, Maecker H, Hunt P, Steen H, Diray-Arce J, Langelier CR, and Melamed E
Abstract: Chronic viral infections are ubiquitous in humans, with individuals harboring multiple latent viruses that can reactivate during acute illnesses. Recent studies have suggested that SARS-CoV-2 infection can lead to reactivation of latent viruses such as Epstein-Barr Virus (EBV) and cytomegalovirus (CMV), yet, the extent and impact of viral reactivation in COVID-19 and its effect on the host immune system remain incompletely understood. Here we present a comprehensive multi-omic analysis of viral reactivation of all known chronically infecting viruses in 1,154 hospitalized COVID-19 patients, from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, who were followed prospectively for twelve months. We reveal significant reactivation of Herpesviridae , Enteroviridae , and Anelloviridae families during acute stage of COVID-19 (0-40 days post-hospitalization), each exhibiting distinct temporal dynamics. We also show that viral reactivation correlated with COVID-19 severity, demographic characteristics, and clinical outcomes, including mortality. Integration of cytokine profiling, cellular immunophenotyping, metabolomics, transcriptomics, and proteomics demonstrated virus-specific host responses, including elevated pro-inflammatory cytokines (e.g. IL-6, CXCL10, and TNF), increased activated CD4+ and CD8+ T-cells, and upregulation of cellular replication genes, independent of COVID-19 severity and SARS-CoV-2 viral load. Notably, persistent Anelloviridae reactivation during convalescence (≥3 months post-hospitalization) was associated with Post-Acute Sequelae of COVID-19 (PASC) symptoms, particularly physical function and fatigue. Our findings highlight a remarkable prevalence and potential impact of chronic viral reactivation on host responses and clinical outcomes during acute COVID-19 and long term PASC sequelae. Our data provide novel immune, transcriptomic, and metabolomic biomarkers of viral reactivation that may inform novel approaches to prognosticate, prevent, or treat acute COVID-19 and PASC., Competing Interests: IMPACC Network Competing Interests The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines which list Florian Krammer as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. Florian Krammer has consulted for Merck and Pfizer (before 2020), and is currently consulting for Pfizer, Seqirus, 3rd Rock Ventures, Merck and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. Viviana Simon is a co-inventor on a patent filed relating to SARS-CoV-2 serological assays (the “Serology Assays”). Ofer Levy is a named inventor on patents held by Boston Children’s Hospital relating to vaccine adjuvants and human in vitro platforms that model vaccine action. His laboratory has received research support from GlaxoSmithKline (GSK) and is a co-founder of and advisor to Ovax, Inc. Charles Cairns serves as a consultant to bioMerieux and is funded for a grant from Bill & Melinda Gates Foundation. James A Overton is a consultant at Knocean Inc. Jessica Lasky-Su serves as a scientific advisor of Precion Inc. Scott R. Hutton, Greg Michelloti and Kari Wong are employees of Metabolon Inc. Vicki Seyfert-Margolis is a current employee of MyOwnMed. Nadine Rouphael reports grants or contracts with Merck, Sanofi, Pfizer, Vaccine Company, Quidel, Lilly and Immorna, and has participated on data safety monitoring boards for Moderna, Sanofi, Seqirus, Pfizer, EMMES, ICON, BARDA, Imunon, CyanVac and Micron. Nadine Rouphael has also received support for meetings/travel from Sanofi and Moderna and honoraria from Virology Education. Adeeb Rahman is a current employee of Immunai Inc. Steven Kleinstein is a consultant related to ImmPort data repository for Peraton. Nathan Grabaugh is a consultant for Tempus Labs and the National Basketball Association. Akiko Iwasaki is a consultant for 4BIO, Blue Willow Biologics, Revelar Biotherapeutics, RIGImmune, Xanadu Bio, Paratus Sciences. Monika Kraft receives research funds paid to her institution from NIH, ALA; Sanofi, Astra-Zeneca for work in asthma, serves as a consultant for Astra-Zeneca, Sanofi, Chiesi, GSK for severe asthma; is a co-founder and CMO for RaeSedo, Inc, a company created to develop peptidomimetics for treatment of inflammatory lung disease. Esther Melamed received research funding from Babson Diagnostics and honorarium from Multiple Sclerosis Association of America and has served on the advisory boards of Genentech, Horizon, Teva, and Viela Bio. Carolyn Calfee receives research funding from NIH, FDA, DOD, Roche-Genentech and Quantum Leap Healthcare Collaborative as well as consulting services for Janssen, Vasomune, Gen1e Life Sciences, NGMBio, and Cellenkos. Wade Schulz was an investigator for a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; is a technical consultant to Hugo Health, a personal health information platform; cofounder of Refactor Health, an AI-augmented data management platform for health care; and has received grants from Merck and Regeneron Pharmaceutical for research related to COVID-19. Grace A McComsey received research grants from Redhill, Cognivue, Pfizer, and Genentech, and served as a research consultant for Gilead, Merck, Viiv/GSK, and Jenssen. Linda N. Geng received research funding paid to her institution from Pfizer, Inc.
Published: 2024
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46. High Rates of High-risk HPV Anal Infection and Abnormal Cytology in a Cohort of Transgender People Assigned Male at Birth.

Author: Harfouch O, Lisco A, Omari H, Eyasu R, Davis A, Zoltick M, Ebah E, Cover A, Bijole P, Silk R, Sternberg D, Liu T, Garrett G, Jones M, Kier R, Masur H, Kottilil S, Kattakuzhy S, and Rosenthal ES
Abstract: Background: Transgender people assigned male at birth (TG-AMAB) have higher rates of anal human papillomavirus (HPV) infection and anal cancer compared with cisgender populations. In a cohort of TG-AMAB in Washington DC, we determined the prevalence and epidemiological factors associated with anal high-risk HPV (HR-HPV) infection and cytological abnormalities., Methods: In an urban academic-community clinic, we recruited adults identifying as a gender different than their sex assigned at birth. Participants provided blood samples, anal swabs for HR-HPV and cytology, and completed surveys on sexual behaviors and use of gender-affirming hormones. Logistic regression was used to identify predictors of HR-HPV and abnormal cytology., Results: Of 97 TG, 80 were AMAB, of whom 66% were people with HIV (PWH); 73% tested positive for any anal HR-HPV, and 48% had abnormal cytology. Only 24% recalled HPV immunization. While TG-AMAB PWH had increased risk of HPV16 infection (37% vs 8%; P = .014), the prevalence rates of any HR-HPV (80% vs 62%; P = .097) and abnormal cytology (56% vs 32%; P = .085) were similarly elevated regardless of HIV status. Among TG-AMAB, estradiol use was not associated with increased odds of any HR-HPV or abnormal cytology (all P > .05); however, higher testosterone levels were associated with any HR-HPV ( P = .014). Age ≥35 years was associated with abnormal cytology in TG-AMAB (59% vs 34%; P = .035)., Conclusions: TG-AMAB have a high prevalence of any HR-HPV and abnormal cytology, regardless of age, HIV status, or hormone use. Given high risk for anal cancer and low rates of HPV vaccination, there is a pressing need for primary and secondary anal cancer prevention strategies targeting this population., Competing Interests: Potential conflicts of interest. S. Kottilil reports grants and other support from the CDA Foundation, Gilead Sciences, Orsobio, and Red Queen Therapeutics. E. Rosenthal reports grants and nonfinancial support from Gilead Sciences and Merck. A. Lisco reports nonfinancial support from Merck. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)
Published: 2024
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47. The Scientific and Therapeutic Rationale for Off-Label Treatments in Amyotrophic Lateral Sclerosis.

Author: Bedlack R, Li X, Evangelista BA, Panzetta ME, Kwan J, Gittings LM, and Sattler R
Abstract: There are no dramatically effective pharmacological treatments for most patients with amyotrophic lateral sclerosis, a complex disease with multiple underlying mechanisms, such as neuroinflammation, oxidative stress, mitochondrial dysfunction, microbiome alteration, and antiretroviral activity. We sifted through 15 years of reviews by a group called ALSUntangled to identify 8 alternative and off-label treatments that target ≥1 of these mechanisms, and have ≥1 human trial suggesting meaningful benefits. Given the overlapping pathological mechanisms of the highlighted products, we suggest that combinations of these treatments targeting diverse mechanisms might be worthwhile for future amyotrophic lateral sclerosis therapy development. ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Published: 2024
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48. Factors associated with diabetes mellitus and hypertension among adults in the northern rural area, Afghanistan.

Author: Fayaz SH, Hamajima N, Frozanfar MK, Hamrah MH, Inthaphatha S, Nishino K, and Yamamoto E
Subjects: Humans, Male, Middle Aged, Adult, Female, Afghanistan epidemiology, Cross-Sectional Studies, Adolescent, Aged, Young Adult, Prevalence, Risk Factors, Waist Circumference, Life Style, Exercise, Hypertension epidemiology, Diabetes Mellitus epidemiology, Rural Population statistics & numerical data
Abstract: Afghanistan has an increasing trend of mortality due to non-communicable diseases but most studies were conducted in urban areas. This study aimed to assess the prevalence and factors associated with diabetes mellitus and hypertension in a rural area in Afghanistan. A cross-sectional study was conducted from September to October 2019 including 373 people who were 18-79 years old and lived in Andkhoy District, Afghanistan. Demographic and lifestyle data was collected by face-to-face interviews after informed consent was obtained. Height, body weight, blood pressure, waist circumference, and blood sugar level were measured by the data collection team. A logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The prevalence of diabetes mellitus and hypertension was 9.7% and 29.5%, respectively. Factors associated with diabetes mellitus were male gender (adjusted OR [AOR]=9.81, 95% CI: 2.48-38.90), family history of diabetes mellitus (AOR=3.84, 95% CI: 1.30-11.38), low physical activity (AOR=4.53, 95% CI: 1.13-18.26), and high waist circumference (AOR=7.93, 95% CI: 2.40-26.20). Snuff users were negatively associated with diabetes mellitus (AOR=0.18, 95% CI: 0.04-0.75). Factors associated with hypertension were the age group of 40-59 years (AOR=4.22, 95% CI: 1.99-8.95) and 60-79 years (AOR=19.83, 95% CI: 7.19-54.71) compared to 18-39 years, family history of hypertension (AOR=2.17, 95% CI: 1.15-4.10), and palaw intake of 3 times per week or more (AOR=1.86, 95% CI: 1.03-3.38). Lifestyle interventions for increasing physical activity should be introduced and health education about snuff usage and salt intake should be promoted in communities in Afghanistan., Competing Interests: No conflicts of interest are declared.
Published: 2024
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49. Role of allogeneic hematopoietic cell transplantation in VEXAS syndrome.

Author: Dias AL, Groarke EM, Hickstein D, and Patel B
Subjects: Humans, Ubiquitin-Activating Enzymes genetics, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes genetics, Transplantation, Homologous, Allografts, Hematopoietic Stem Cell Transplantation
Abstract: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a newly diagnosed syndrome comprising severe systemic inflammatory and hematological manifestations including myelodysplastic syndrome and plasma cell dyscrasia. Since its discovery four years ago, several groups have identified pleomorphic clinical phenotypes, but few effective medical therapies exist which include Janus Kinase (JAK) inhibitors, interleukin inhibitors (IL-1 and IL-6), and hypomethylating agents. Prospective trials are lacking at this time and most patients remain corticosteroid dependent. VEXAS has a high morbidity from frequent life threatening inflammatory symptoms and risk of progression to hematological malignancies and has an overall survival of 50% at 10 years. Allogeneic stem cell transplant (allo-HCT) is a curative option for this disease caused by somatic mutations in the UBA1 gene. Here we outline the role of allo-HCT in treating patients with VEXAS syndrome, highlighting the outcomes from several single-institution studies and case reports. Prospective trials will be required to precisely define the role of allo-HCT in the management of VEXAS syndrome., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Published: 2024
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50. Linking Protein Stability to Pathogenicity: Predicting Clinical Significance of Single-Missense Mutations in Ocular Proteins Using Machine Learning.

Author: Majid I and Sergeev YV
Subjects: Humans, Eye Proteins genetics, Eye Proteins chemistry, Eye Proteins metabolism, cis-trans-Isomerases genetics, cis-trans-Isomerases metabolism, cis-trans-Isomerases chemistry, Eye Diseases genetics, Clinical Relevance, Machine Learning, Protein Stability, Mutation, Missense
Abstract: Understanding the effect of single-missense mutations on protein stability is crucial for clinical decision-making and therapeutic development. The impact of these mutations on protein stability and 3D structure remains underexplored. Here, we developed a program to investigate the relationship between pathogenic mutations with protein unfolding and compared seven machine learning (ML) models to predict the clinical significance of single-missense mutations with unknown impacts, based on protein stability parameters. We analyzed seven proteins associated with ocular disease-causing genes. The program revealed an R-squared value of 0.846 using Decision Tree Regression between pathogenic mutations and decreased protein stability, with 96.20% of pathogenic mutations in RPE65 leading to protein instability. Among the ML models, Random Forest achieved the highest AUC (0.922) and PR AUC (0.879) in predicting the clinical significance of mutations with unknown effects. Our findings indicate that most pathogenic mutations affecting protein stability occur in alpha-helices, beta-pleated sheets, and active sites. This study suggests that protein stability can serve as a valuable parameter for interpreting the clinical significance of single-missense mutations in ocular proteins.
Published: 2024
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