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Parkinson Disease: HELP
Articles by Philip L. De Jager
Based on 6 articles published since 2010
(Why 6 articles?)
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Between 2010 and 2020, Philip L. De Jager wrote the following 6 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Review Parkinson's disease: genetics and pathogenesis. 2011

Shulman, Joshua M / De Jager, Philip L / Feany, Mel B. ·Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA. jshulman2@partners.org ·Annu Rev Pathol · Pubmed #21034221.

ABSTRACT: Recent investigation into the mechanisms of Parkinson's disease (PD) has generated remarkable insight while simultaneously challenging traditional conceptual frameworks. Although the disease remains defined clinically by its cardinal motor manifestations and pathologically by midbrain dopaminergic cell loss in association with Lewy bodies, it is now recognized that PD has substantially more widespread impact, causing a host of nonmotor symptoms and associated pathology in multiple regions throughout the nervous system. Further, the discovery and validation of PD-susceptibility genes contradict the historical view that environmental factors predominate, and blur distinctions between familial and sporadic disease. Genetic advances have also promoted the development of improved animal models, highlighted responsible molecular pathways, and revealed mechanistic overlap with other neurodegenerative disorders. In this review, we synthesize emerging lessons on PD pathogenesis from clinical, pathological, and genetic studies toward a unified concept of the disorder that may accelerate the design and testing of the next generation of PD therapies.

2 Article Polygenic analysis of inflammatory disease variants and effects on microglia in the aging brain. 2018

Felsky, Daniel / Patrick, Ellis / Schneider, Julie A / Mostafavi, Sara / Gaiteri, Chris / Patsopoulos, Nikolaos / Bennett, David A / De Jager, Philip L. ·Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, 630 West 168th Street, PH 19 - 302, New York, NY, 10032, USA. df2652@columbia.edu. · Department of Neurology, Brigham and Woman's Hospital, 75 Francis Street, Boston, MA, 02115, USA. df2652@columbia.edu. · Department of Neurology, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA. df2652@columbia.edu. · Program in Population and Medical Genetics, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA. df2652@columbia.edu. · Department of Statistics, University of Sydney, Camperdown, NSW, 2006, Australia. · Department of Neurology, Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL, 60612, USA. · Rush Alzheimer's Disease Center, Rush University Medical Center, 600 South Paulina Street, Chicago, IL, 60612, USA. · Department of Statistics, University of British Columbia, 2329 West Mall, Vancouver, BC, V6T 1Z4, Canada. · Department of Neurology, Brigham and Woman's Hospital, 75 Francis Street, Boston, MA, 02115, USA. · Department of Neurology, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA. · Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, 630 West 168th Street, PH 19 - 302, New York, NY, 10032, USA. · Program in Population and Medical Genetics, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA. ·Mol Neurodegener · Pubmed #30041668.

ABSTRACT: BACKGROUND: The role of the innate immune system in Alzheimer's disease (AD) and neurodegenerative disease susceptibility has recently been highlighted in genetic studies. However, we do not know whether risk for inflammatory disease predisposes unaffected individuals to late-life cognitive deficits or AD-related neuropathology. We investigated whether genetic risk scores for seven immune diseases and central nervous system traits were related to cognitive decline (n METHODS: Longitudinal cognitive decline, postmortem amyloid and tau neuropathology, microglial density, and gene module expression from bulk brain tissue were all measured in participants from two large cohorts (the Rush Religious Orders Study and Memory and Aging Project; ROS/MAP) of elderly subjects (mean age at entry 78 +/- 8.7 years). We analyzed data primarily using robust regression methods. Neuropathologists were blind to clinical data. RESULTS: The AD genetic risk scores, including and excluding APOE effects, were strongly associated with cognitive decline in all domains (min P CONCLUSIONS: Our results demonstrate that global risk of inflammatory disease does not strongly influence aging-related cognitive decline but that susceptibility variants that influence peripheral immune function also alter microglial density and immune gene expression in the aging brain, opening a new perspective on the control of microglial and immune responses within the central nervous system. Further study on the molecular mechanisms of peripheral immune disease risk influencing glial cell activation will be required to identify key regulators of these pathways.

3 Article Novel genetic loci underlying human intracranial volume identified through genome-wide association. 2016

Adams, Hieab H H / Hibar, Derrek P / Chouraki, Vincent / Stein, Jason L / Nyquist, Paul A / Rentería, Miguel E / Trompet, Stella / Arias-Vasquez, Alejandro / Seshadri, Sudha / Desrivières, Sylvane / Beecham, Ashley H / Jahanshad, Neda / Wittfeld, Katharina / Van der Lee, Sven J / Abramovic, Lucija / Alhusaini, Saud / Amin, Najaf / Andersson, Micael / Arfanakis, Konstantinos / Aribisala, Benjamin S / Armstrong, Nicola J / Athanasiu, Lavinia / Axelsson, Tomas / Beiser, Alexa / Bernard, Manon / Bis, Joshua C / Blanken, Laura M E / Blanton, Susan H / Bohlken, Marc M / Boks, Marco P / Bralten, Janita / Brickman, Adam M / Carmichael, Owen / Chakravarty, M Mallar / Chauhan, Ganesh / Chen, Qiang / Ching, Christopher R K / Cuellar-Partida, Gabriel / Braber, Anouk Den / Doan, Nhat Trung / Ehrlich, Stefan / Filippi, Irina / Ge, Tian / Giddaluru, Sudheer / Goldman, Aaron L / Gottesman, Rebecca F / Greven, Corina U / Grimm, Oliver / Griswold, Michael E / Guadalupe, Tulio / Hass, Johanna / Haukvik, Unn K / Hilal, Saima / Hofer, Edith / Hoehn, David / Holmes, Avram J / Hoogman, Martine / Janowitz, Deborah / Jia, Tianye / Kasperaviciute, Dalia / Kim, Sungeun / Klein, Marieke / Kraemer, Bernd / Lee, Phil H / Liao, Jiemin / Liewald, David C M / Lopez, Lorna M / Luciano, Michelle / Macare, Christine / Marquand, Andre / Matarin, Mar / Mather, Karen A / Mattheisen, Manuel / Mazoyer, Bernard / McKay, David R / McWhirter, Rebekah / Milaneschi, Yuri / Mirza-Schreiber, Nazanin / Muetzel, Ryan L / Maniega, Susana Muñoz / Nho, Kwangsik / Nugent, Allison C / Loohuis, Loes M Olde / Oosterlaan, Jaap / Papmeyer, Martina / Pappa, Irene / Pirpamer, Lukas / Pudas, Sara / Pütz, Benno / Rajan, Kumar B / Ramasamy, Adaikalavan / Richards, Jennifer S / Risacher, Shannon L / Roiz-Santiañez, Roberto / Rommelse, Nanda / Rose, Emma J / Royle, Natalie A / Rundek, Tatjana / Sämann, Philipp G / Satizabal, Claudia L / Schmaal, Lianne / Schork, Andrew J / Shen, Li / Shin, Jean / Shumskaya, Elena / Smith, Albert V / Sprooten, Emma / Strike, Lachlan T / Teumer, Alexander / Thomson, Russell / Tordesillas-Gutierrez, Diana / Toro, Roberto / Trabzuni, Daniah / Vaidya, Dhananjay / Van der Grond, Jeroen / Van der Meer, Dennis / Van Donkelaar, Marjolein M J / Van Eijk, Kristel R / Van Erp, Theo G M / Van Rooij, Daan / Walton, Esther / Westlye, Lars T / Whelan, Christopher D / Windham, Beverly G / Winkler, Anderson M / Woldehawariat, Girma / Wolf, Christiane / Wolfers, Thomas / Xu, Bing / Yanek, Lisa R / Yang, Jingyun / Zijdenbos, Alex / Zwiers, Marcel P / Agartz, Ingrid / Aggarwal, Neelum T / Almasy, Laura / Ames, David / Amouyel, Philippe / Andreassen, Ole A / Arepalli, Sampath / Assareh, Amelia A / Barral, Sandra / Bastin, Mark E / Becker, Diane M / Becker, James T / Bennett, David A / Blangero, John / van Bokhoven, Hans / Boomsma, Dorret I / Brodaty, Henry / Brouwer, Rachel M / Brunner, Han G / Buckner, Randy L / Buitelaar, Jan K / Bulayeva, Kazima B / Cahn, Wiepke / Calhoun, Vince D / Cannon, Dara M / Cavalleri, Gianpiero L / Chen, Christopher / Cheng, Ching-Yu / Cichon, Sven / Cookson, Mark R / Corvin, Aiden / Crespo-Facorro, Benedicto / Curran, Joanne E / Czisch, Michael / Dale, Anders M / Davies, Gareth E / De Geus, Eco J C / De Jager, Philip L / de Zubicaray, Greig I / Delanty, Norman / Depondt, Chantal / DeStefano, Anita L / Dillman, Allissa / Djurovic, Srdjan / Donohoe, Gary / Drevets, Wayne C / Duggirala, Ravi / Dyer, Thomas D / Erk, Susanne / Espeseth, Thomas / Evans, Denis A / Fedko, Iryna O / Fernández, Guillén / Ferrucci, Luigi / Fisher, Simon E / Fleischman, Debra A / Ford, Ian / Foroud, Tatiana M / Fox, Peter T / Francks, Clyde / Fukunaga, Masaki / Gibbs, J Raphael / Glahn, David C / Gollub, Randy L / Göring, Harald H H / Grabe, Hans J / Green, Robert C / Gruber, Oliver / Gudnason, Vilmundur / Guelfi, Sebastian / Hansell, Narelle K / Hardy, John / Hartman, Catharina A / Hashimoto, Ryota / Hegenscheid, Katrin / Heinz, Andreas / Le Hellard, Stephanie / Hernandez, Dena G / Heslenfeld, Dirk J / Ho, Beng-Choon / Hoekstra, Pieter J / Hoffmann, Wolfgang / Hofman, Albert / Holsboer, Florian / Homuth, Georg / Hosten, Norbert / Hottenga, Jouke-Jan / Hulshoff Pol, Hilleke E / Ikeda, Masashi / Ikram, M Kamran / Jack, Clifford R / Jenkinson, Mark / Johnson, Robert / Jönsson, Erik G / Jukema, J Wouter / Kahn, René S / Kanai, Ryota / Kloszewska, Iwona / Knopman, David S / Kochunov, Peter / Kwok, John B / Lawrie, Stephen M / Lemaître, Hervé / Liu, Xinmin / Longo, Dan L / Longstreth, W T / Lopez, Oscar L / Lovestone, Simon / Martinez, Oliver / Martinot, Jean-Luc / Mattay, Venkata S / McDonald, Colm / McIntosh, Andrew M / McMahon, Katie L / McMahon, Francis J / Mecocci, Patrizia / Melle, Ingrid / Meyer-Lindenberg, Andreas / Mohnke, Sebastian / Montgomery, Grant W / Morris, Derek W / Mosley, Thomas H / Mühleisen, Thomas W / Müller-Myhsok, Bertram / Nalls, Michael A / Nauck, Matthias / Nichols, Thomas E / Niessen, Wiro J / Nöthen, Markus M / Nyberg, Lars / Ohi, Kazutaka / Olvera, Rene L / Ophoff, Roel A / Pandolfo, Massimo / Paus, Tomas / Pausova, Zdenka / Penninx, Brenda W J H / Pike, G Bruce / Potkin, Steven G / Psaty, Bruce M / Reppermund, Simone / Rietschel, Marcella / Roffman, Joshua L / Romanczuk-Seiferth, Nina / Rotter, Jerome I / Ryten, Mina / Sacco, Ralph L / Sachdev, Perminder S / Saykin, Andrew J / Schmidt, Reinhold / Schofield, Peter R / Sigurdsson, Sigurdur / Simmons, Andy / Singleton, Andrew / Sisodiya, Sanjay M / Smith, Colin / Smoller, Jordan W / Soininen, Hilkka / Srikanth, Velandai / Steen, Vidar M / Stott, David J / Sussmann, Jessika E / Thalamuthu, Anbupalam / Tiemeier, Henning / Toga, Arthur W / Traynor, Bryan J / Troncoso, Juan / Turner, Jessica A / Tzourio, Christophe / Uitterlinden, Andre G / Hernández, Maria C Valdés / Van der Brug, Marcel / Van der Lugt, Aad / Van der Wee, Nic J A / Van Duijn, Cornelia M / Van Haren, Neeltje E M / Van T Ent, Dennis / Van Tol, Marie-Jose / Vardarajan, Badri N / Veltman, Dick J / Vernooij, Meike W / Völzke, Henry / Walter, Henrik / Wardlaw, Joanna M / Wassink, Thomas H / Weale, Michael E / Weinberger, Daniel R / Weiner, Michael W / Wen, Wei / Westman, Eric / White, Tonya / Wong, Tien Y / Wright, Clinton B / Zielke, H Ronald / Zonderman, Alan B / Deary, Ian J / DeCarli, Charles / Schmidt, Helena / Martin, Nicholas G / De Craen, Anton J M / Wright, Margaret J / Launer, Lenore J / Schumann, Gunter / Fornage, Myriam / Franke, Barbara / Debette, Stéphanie / Medland, Sarah E / Ikram, M Arfan / Thompson, Paul M / and others. ·Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. · Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands. · Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, Los Angeles, California, USA. · Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA. · Lille University, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE - Risk factors and molecular determinants of aging-related diseases, Lille, France. · Framingham Heart Study, Framingham, Massachusetts, USA. · Department of Genetics and UNC Neuroscience Center, University of North Carolina (UNC), Chapel Hill, North Carolina, USA. · Department of Neurology, Department of Anesthesia/Critical Care Medicine, Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland, USA. · QIMR Berghofer Medical Research Institute, Brisbane, Australia. · Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands. · Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands. · Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands. · Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands. · Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands. · MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. · Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, Florida, USA. · John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA. · German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald, Germany. · Department of Psychiatry, University Medicine Greifswald, Greifswald, Germany. · Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht, the Netherlands. · Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada. · The Royal College of Surgeons in Ireland, Dublin 2, Ireland. · Department of Integrative Medical Biology and Umeå center for Functional Brain Imaging, Umeå University, Umeå, Sweden. · Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, USA. · Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA. · Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, Illinois, USA. · Brain Research Imaging Centre, University of Edinburgh, Edinburgh, 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, UK. · Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia. · Mathematics and Statistics, Murdoch University, Perth, Australia. · NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. · Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. · Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA. · Hospital for Sick Children, University of Toronto, Toronto, Canada. · Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA. · Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands. · Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA. · G.H. Sergievsky Center, Columbia University Medical Center, New York, New York, USA. · Department of Neurology, Columbia University Medical Center, New York, New York, USA. · Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA. · Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada. · Department of Psychiatry and Biomedical Engineering, McGill University, Montreal, Canada. · INSERM Unit U1219, University of Bordeaux, France. · Lieber Institute for Brain Development, Baltimore, Maryland, USA. · Interdepartmental Neuroscience Graduate Program, UCLA School of Medicine, Los Angeles, California, USA. · Biological Psychology, Neuroscience Campus Amsterdam, Vrije Universiteit University and Vrije Universiteit Medical Center, Amsterdam, the Netherlands. · Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Germany. · Department of Psychiatry, Massachusetts General Hospital, Boston, Masschusetts, USA. · Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, North Carolina, USA. · NSERM Unit 1000 ″Neuroimaging and Psychiatry″, University Paris Sud, University Paris Descartes, Paris, France. · Maison de Solenn, Adolescent Psychopathology and Medicine Department, APHP Hospital Cochin, Paris, France. · Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. · Harvard Medical School, Boston, Massachusetts, USA. · Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts, USA. · NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Norway. · Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway. · Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Karakter Child and Adolescent Psychiatry University Center, Nijmegen, the Netherlands. · King's College London, Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychology, Psychiatry and Neurosciene, London, UK. · Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany. · Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, Mississippi, USA. · Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands. · International Max Planck Research School for Language Sciences, Nijmegen, the Netherlands. · Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden, Germany. · Department of Research and Development, Diakonhjemmet Hospital, Oslo, Norway. · Department of Pharmacology, National University of Singapore, Singapore. · Memory Aging and Cognition Centre (MACC), National University Health System, Singapore. · Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Austria, Graz, Austria. · Institute of Medical Informatics, Statistics and Documentation, Medical University Graz, Austria, Graz, Austria. · Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, Germany. · Department of Psychology, Yale University, New Haven, Connecticut, USA. · UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, Bucks, UK. · Department of Medicine, Imperial College London, London, UK. · Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany. · Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, Lexington, Massachusetts, USA. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh, UK. · Donders Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, The Netherlands. · Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. · Department of Biomedicine, Aarhus University, Aarhus, Denmark. · The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark. · Center for integrated Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. · UMR5296 University of Bordeaux, CNRS, CEA, Bordeaux, France. · Department of Psychiatry, Yale University, New Haven, Connecticut, USA. · Olin Neuropsychiatric Research Center, Hartford, Connecticut, USA. · Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. · Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands. · Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland, USA. · Center for Neurobehavioral Genetics, University of California, Los Angeles, California, USA. · Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, the Netherlands. · Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK. · Division of Systems Neuroscience of Psychopathology, Translational Research Center, University Hospital of Psychiatry, University of Bern, Switzerland. · School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, Rotterdam, the Netherlands. · Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, Illinois, USA. · Department of Medical and Molecular Genetics, King's College London, London, UK. · The Jenner Institute Laboratories, University of Oxford, Oxford, UK. · Department of Medicine and Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander, Spain. · CIBERSAM (Centro Investigación Biomédica en Red Salud Mental), Santander, Spain. · Psychosis Research Group, Department of Psychiatry and Trinity Translational Medicine Institute, Trinity College Dublin. · Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. · Department of Neurology, University of Miami, Miller School of Medicine, Miami, Florida, USA. · Department of Epidemiology and Public Health Sciences, University of Miami, Miller School of Medicine, Miami, Florida, USA. · Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia. · Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia. · Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands. · Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, USA. · Department of Cognitive Sciences, University of California, San Diego, USA. · Icelandic Heart Association, Kopavogur, Iceland. · Faculty of Medicine, University of Iceland, Reykjavik, Iceland. · Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA. · Queensland Brain Institute, University of Queensland, Brisbane, Australia. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. · School of Computing Engineering and Mathematics, Western Sydney University, Parramatta, Australia. · Neuroimaging Unit,Technological Facilities. Valdecilla Biomedical Research Institute IDIVAL, Santander, Cantabria, Spain. · Institut Pasteur, Paris, France. · Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. · GeneSTAR Research Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands. · Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. · Brain Center Rudolf Magnus, Human Neurogenetics Unit, UMC Utrecht, Utrecht, the Netherlands. · Department of Psychiatry and Human Behavior, University of California-Irvine, Irvine, California, USA. · NORMENT - KG Jebsen Centre, Department of Psychology, University of Oslo, Oslo, Norway. · Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA. · FMRIB Centre, University of Oxford, Oxford, UK. · University of Wuerzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, Wuerzburg, Germany. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. · Biospective Inc, Montreal, Quebec, Canada, Montréal, Québec, Canada. · Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden. · South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine Brownsville/Edinburg/San Antonio, Texas, USA. · Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. · National Ageing Research Institute, Royal Melbourne Hospital, Melbourne, Australia. · Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne, Australia. · Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA. · Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Dementia Collaborative Research Centre - Assessment and Better Care, UNSW, Sydney, Australia. · Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands. · Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA. · Department of Evolution and Genetics, Dagestan State University, Makhachkala, Dagestan, Russia. · The Mind Research Network and LBERI, Albuquerque, New Mexico, USA. · Department of ECE, University of New Mexico, Albuquerque, New Mexico, USA. · Centre for Neuroimaging and Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. · Academic Medicine Research Institute, Duke-NUS Graduate Medical School, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland. · Institute of Human Genetics, University of Bonn, Bonn, Germany. · Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany. · Center for Multimodal Imaging and Genetics, University of California, San Diego, California, USA. · Department of Neurosciences, University of California, San Diego, California, USA. · Department of Radiology, University of California, San Diego, California, USA. · Department of Psychiatry, University of California, San Diego, California, USA. · Department of Cognitive Science, University of California, San Diego, California, USA. · Avera Institute for Human Genetics, Sioux Falls, South Dakota, USA. · Program in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. · Broad Institute, Cambridge, Massachusetts, USA. · Faculty of Health and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Australia. · Neurology Division, Beaumont Hospital, Dublin, 9, Ireland. · Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium. · Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. · Cognitive Genetics and Cognitive Therapy Group, Neuroimaging, Cognition and Genomics Centre (NICOG) and NCBES Galway Neuroscience Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland. · Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 8, Ireland. · Janssen Research and Development, LLC, Titusville, New Jersey, USA. · Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin, Germany. · Intramural Research Program of the National Institute on Aging, Baltimore, Maryland, USA. · Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, USA. · Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK. · Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA. · University of Texas Health Science Center, San Antonio, Texas, USA. · Division of Cerebral Integration, National Institute for Physiological Sciences, Aichi, Japan. · Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan. · Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan. · Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany. · German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. · Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands. · Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA. · HMNC Brain Health, Munich, Germany. · Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. · Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan. · Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA. · NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland, USA. · School of Psychology, University of Sussex, Brighton, UK. · Institute of Cognitive Neuroscience, University College London, London, UK. · Department of Neuroinformatics, Araya Brain Imaging, Tokyo, Japan. · Medical University of Lodz, Lodz, Poland. · Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA. · Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA. · Neuroscience Research Australia, Sydney, Australia. · School of Medical Sciences, UNSW, Sydney, Australia. · Columbia University Medical Center, New York, New York, USA. · Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA. · Department of Neurology, University of Washington, Seattle, Washington, USA. · Department of Epidemiology, University of Washington, Seattle, Washington, USA. · Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Department of Psychiatry, University of Oxford, Oxford, UK. · NIHR Dementia Biomedical Research Unit, King's College London, London, UK. · Imaging of Dementia and Aging (IDeA) Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, California, USA. (and more) ·Nat Neurosci · Pubmed #27694991.

ABSTRACT: 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 (ρ

4 Article The Role of MAPT Haplotype H2 and Isoform 1N/4R in Parkinsonism of Older Adults. 2016

Valenca, Guilherme T / Srivastava, Gyan P / Oliveira-Filho, Jamary / White, Charles C / Yu, Lei / Schneider, Julie A / Buchman, Aron S / Shulman, Joshua M / Bennett, David A / De Jager, Philip L. ·Movement Disorders Clinic, Roberto Santos General Hospital, Salvador, BA, Brazil. · Health Sciences Center, Federal University of Reconcavo of Bahia, Santo Antonio de Jesus, BA, Brazil. · Post-Graduate Program in Health Sciences, Federal University of Bahia, Salvador, BA, Brazil. · Program in Translational Neuropsychiatric Genomics, Departments of Neurology & Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, United States of America. · Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America. · Harvard Medical School, Boston, Massachusetts, United States of America. · Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States of America. · Departments of Neurology, Molecular and Human Genetics, and Neuroscience, and Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America. · Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, United States of America. ·PLoS One · Pubmed #27458716.

ABSTRACT: BACKGROUND AND OBJECTIVE: Recently, we have shown that the Parkinson's disease (PD) susceptibility locus MAPT (microtubule associated protein tau) is associated with parkinsonism in older adults without a clinical diagnosis of PD. In this study, we investigated the relationship between parkinsonian signs and MAPT transcripts by assessing the effect of MAPT haplotypes on alternative splicing and expression levels of the most common isoforms in two prospective clinicopathologic studies of aging. MATERIALS AND METHODS: using regression analysis, controlling for age, sex, study and neuropathology, we evaluated 976 subjects with clinical, genotyping and brain pathology data for haplotype analysis. For transcript analysis, we obtained MAPT gene and isoform-level expression from the dorsolateral prefrontal cortex for 505 of these subjects. RESULTS: The MAPT H2 haplotype was associated with lower total MAPT expression (p = 1.2x10-14) and global parkinsonism at both study entry (p = 0.001) and proximate to death (p = 0.050). Specifically, haplotype H2 was primarily associated with bradykinesia in both assessments (p<0.001 and p = 0.008). MAPT total expression was associated with age and decreases linearly with advancing age (p<0.001). Analysing MAPT alternative splicing, the expression of 1N/4R isoform was inversely associated with global parkinsonism (p = 0.008) and bradykinesia (p = 0.008). Diminished 1N/4R isoform expression was also associated with H2 (p = 0.001). CONCLUSIONS: Overall, our results suggest that age and H2 are associated with higher parkinsonism score and decreased total MAPT RNA expression. Additionally, we found that H2 and parkinsonism are associated with altered expression levels of specific isoforms. These findings may contribute to the understanding of the association between MAPT locus and parkinsonism in elderly subjects and in some extent to age-related neurodegenerative diseases.

5 Article Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes. 2014

Raj, Towfique / Rothamel, Katie / Mostafavi, Sara / Ye, Chun / Lee, Mark N / Replogle, Joseph M / Feng, Ting / Lee, Michelle / Asinovski, Natasha / Frohlich, Irene / Imboywa, Selina / Von Korff, Alina / Okada, Yukinori / Patsopoulos, Nikolaos A / Davis, Scott / McCabe, Cristin / Paik, Hyun-il / Srivastava, Gyan P / Raychaudhuri, Soumya / Hafler, David A / Koller, Daphne / Regev, Aviv / Hacohen, Nir / Mathis, Diane / Benoist, Christophe / Stranger, Barbara E / De Jager, Philip L. ·Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, MA 02115, USA. ·Science · Pubmed #24786080.

ABSTRACT: To extend our understanding of the genetic basis of human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study of purified CD4(+) T cells and monocytes, representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. Context-specific cis- and trans-eQTLs were identified, and cross-population mapping allowed, in some cases, putative functional assignment of candidate causal regulatory variants for disease-associated loci. We note an over-representation of T cell-specific eQTLs among susceptibility alleles for autoimmune diseases and of monocyte-specific eQTLs among Alzheimer's and Parkinson's disease variants. This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants.

6 Article Association of Parkinson disease risk loci with mild parkinsonian signs in older persons. 2014

Shulman, Joshua M / Yu, Lei / Buchman, Aron S / Evans, Denis A / Schneider, Julie A / Bennett, David A / De Jager, Philip L. ·Department of Neurology, Baylor College of Medicine, Houston, Texas2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas3Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston. · Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois. · Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, Illinois. · Program in Translational Neuropsychiatric Genomics, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts7Harvard Medical School, Boston, Massachusetts8Program in Medical and Population Genetics, Broad Institute, Cam. ·JAMA Neurol · Pubmed #24514572.

ABSTRACT: IMPORTANCE: Parkinsonian motor signs are common in the aging population and are associated with adverse health outcomes. Compared with Parkinson disease (PD), potential genetic risk factors for mild parkinsonian signs have been largely unexplored. OBJECTIVE: To determine whether PD susceptibility loci are associated with parkinsonism or substantia nigra pathology in a large community-based cohort of older persons. DESIGN, SETTING, AND PARTICIPANTS: Eighteen candidate single-nucleotide polymorphisms from PD genome-wide association studies were evaluated in a joint clinicopathologic cohort. Participants included 1698 individuals and a nested autopsy collection of 821 brains from the Religious Orders Study and the Rush Memory and Aging Project, 2 prospective community-based studies. MAIN OUTCOMES AND MEASURES: The primary outcomes were a quantitative measure of global parkinsonism or component measures of bradykinesia, rigidity, tremor, and gait impairment that were based on the motor Unified Parkinson's Disease Rating Scale. In secondary analyses, we examined associations with additional quantitative motor traits and postmortem indices, including substantia nigra Lewy bodies and neuronal loss. RESULTS: Parkinson disease risk alleles in the MAPT (rs2942168; P = .0006) and CCDC62 (rs12817488; P = .004) loci were associated with global parkinsonism, and these associations remained after exclusion of patients with a PD diagnosis. Based on motor Unified Parkinson's Disease Rating Scale subscores, MAPT (P = .0002) and CCDC62 (P = .003) were predominantly associated with bradykinesia, and we further discovered associations between SREBF1 (rs11868035; P = .005) and gait impairment, SNCA (rs356220; P = .04) and rigidity, and GAK (rs1564282; P = .03) and tremor. In the autopsy cohort, only NMD3 (rs34016896; P = .03) was related to nigral neuronal loss, and no associations were detected with Lewy bodies. CONCLUSIONS AND RELEVANCE: In addition to the established link to PD susceptibility, our results support a broader role for several loci in the development of parkinsonian motor signs and nigral pathology in older persons.