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Parkinson Disease: HELP
Articles by Andre G. Uitterlinden
Based on 10 articles published since 2010
(Why 10 articles?)
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Between 2010 and 2020, A. G. Uitterlinden wrote the following 10 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Article Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease. 2017

Robak, Laurie A / Jansen, Iris E / van Rooij, Jeroen / Uitterlinden, André G / Kraaij, Robert / Jankovic, Joseph / Anonymous1541133 / Heutink, Peter / Shulman, Joshua M. ·Department of Molecular and Human Genetics, Baylor College of Medicine, Houston TX USA. · Jan and Dan Duncan Neurologic Research Institute, Texas Children's Hospital, Houston TX USA. · German Center for Neurodegenerative Diseases (DZNE) and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen 72076, Germany. · Department of Clinical Genetics, VU University Medical Center, Amsterdam 1081HZ, The Netherlands. · Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. · Netherlands Consortium for Healthy Ageing (NCHA), Rotterdam, The Netherlands. · Department of Neurology, Erasmus MC, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. · Department of Neurology, Baylor College of Medicine, Houston, TX, USA. · Department of Neuroscience and Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA. ·Brain · Pubmed #29140481.

ABSTRACT: Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk. The association signal was robust to the exclusion of GBA, and consistent results were obtained in two independent replication cohorts, including 436 cases and 169 controls with whole exome sequencing and an additional 6713 cases and 5964 controls with exome-wide genotyping. In secondary analyses designed to highlight the specific genes driving the aggregate signal, we confirmed associations at the GBA and SMPD1 loci and newly implicate CTSD, SLC17A5, and ASAH1 as candidate Parkinson's disease susceptibility genes. In our discovery cohort, the majority of Parkinson's disease cases (56%) have at least one putative damaging variant in a lysosomal storage disorder gene, and 21% carry multiple alleles. Our results highlight several promising new susceptibility loci and reinforce the importance of lysosomal mechanisms in Parkinson's disease pathogenesis. We suggest that multiple genetic hits may act in combination to degrade lysosomal function, enhancing Parkinson's disease susceptibility.

2 Article Establishing the role of rare coding variants in known Parkinson's disease risk loci. 2017

Jansen, Iris E / Gibbs, J Raphael / Nalls, Mike A / Price, T Ryan / Lubbe, Steven / van Rooij, Jeroen / Uitterlinden, André G / Kraaij, Robert / Williams, Nigel M / Brice, Alexis / Hardy, John / Wood, Nicholas W / Morris, Huw R / Gasser, Thomas / Singleton, Andrew B / Heutink, Peter / Sharma, Manu / Anonymous350918. ·Department of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands; Genome Biology of Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. · Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA. · Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA; Data Tecnica International, Glen Echo, MD, USA. · University California Irvine, Irvine, CA, USA. · Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. · Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands. · Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Ageing (NCHA), Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. · MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales, UK. · Inserm U1127, CNRS UMR7225, Sorbonne Universités, UPMC Univ Paris 06, UMR_S1127, Institut du Cerveau et de la Moelle épinière, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, Paris, France. · Reta Lila Weston Institute, University College London, London, UK. · Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK. · Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany. · Genome Biology of Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany. · Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany. Electronic address: manu.sharma@uni-tuebingen.de. ·Neurobiol Aging · Pubmed #28867149.

ABSTRACT: Many common genetic factors have been identified to contribute to Parkinson's disease (PD) susceptibility, improving our understanding of the related underlying biological mechanisms. The involvement of rarer variants in these loci has been poorly studied. Using International Parkinson's Disease Genomics Consortium data sets, we performed a comprehensive study to determine the impact of rare variants in 23 previously published genome-wide association studies (GWAS) loci in PD. We applied Prix fixe to select the putative causal genes underneath the GWAS peaks, which was based on underlying functional similarities. The Sequence Kernel Association Test was used to analyze the joint effect of rare, common, or both types of variants on PD susceptibility. All genes were tested simultaneously as a gene set and each gene individually. We observed a moderate association of common variants, confirming the involvement of the known PD risk loci within our genetic data sets. Focusing on rare variants, we identified additional association signals for LRRK2, STBD1, and SPATA19. Our study suggests an involvement of rare variants within several putatively causal genes underneath previously identified PD GWAS peaks.

3 Article Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population. 2017

Giri, Anamika / Mok, Kin Y / Jansen, Iris / Sharma, Manu / Tesson, Christelle / Mangone, Graziella / Lesage, Suzanne / Bras, José M / Shulman, Joshua M / Sheerin, Una-Marie / Anonymous5870886 / Díez-Fairen, Mónica / Pastor, Pau / Martí, María José / Ezquerra, Mario / Tolosa, Eduardo / Correia-Guedes, Leonor / Ferreira, Joaquim / Amin, Najaf / van Duijn, Cornelia M / van Rooij, Jeroen / Uitterlinden, André G / Kraaij, Robert / Nalls, Michael / Simón-Sánchez, Javier. ·Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. · Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. · German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Department of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands. · Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany. · Institut du Cerveau et de la Moelle épinière, ICM, Inserm U 1127, CNRS, UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S 1127, AP-HP, Pitié-Salpêtrière Hospital, Paris, France. · Departments of Neurology and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. · Movement Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Barcelona, Spain. · Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. · Department of Neurosciences, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal. · Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. · Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. · Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Ageing (NCHA), Rotterdam, the Netherlands. · Department of Neurosciences, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal; Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Ageing (NCHA), Rotterdam, the Netherlands. · Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Ageing (NCHA), Rotterdam, the Netherlands. · Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA. · Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. Electronic address: javier.simon-sanchez@dzne.de. ·Neurobiol Aging · Pubmed #27818000.

ABSTRACT: Mutations in TMEM230 have recently been associated to Parkinson's disease (PD). To further understand the role of this gene in the Caucasian population, we interrogated our large repository of next generation sequencing data from unrelated PD cases and controls, as well as multiplex families with autosomal dominant PD. We identified 2 heterozygous missense variants in 2 unrelated PD cases and not in our control database (p.Y106H and p.I162V), and a heterozygous missense variant in 2 PD cases from the same family (p.A163T). However, data presented herein is not sufficient to support the role of any of these variants in PD pathology. A series of unified sequence kernel association tests also failed to show a cumulative effect of rare variation in this gene on the risk of PD in the general Caucasian population. Further evaluation of genetic data from different populations is needed to understand the genetic role of TMEM230 in PD etiology.

4 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

5 Article Genetic risk of Parkinson's disease in the general population. 2016

Darweesh, Sirwan K L / Verlinden, Vincentius J A / Adams, Hieab H H / Uitterlinden, André G / Hofman, Albert / Stricker, Bruno H / van Duijn, Cornelia M / Koudstaal, Peter J / Ikram, M Arfan. ·Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Radiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. · Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Inspectorate for Health Care, The Hague, The Netherlands. · Department of Neurology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Radiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Neurology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: m.a.ikram@erasmusmc.nl. ·Parkinsonism Relat Disord · Pubmed #27269966.

ABSTRACT: INTRODUCTION: We investigated whether a risk score based on genetic risk variants for Parkinson's disease (PD) is associated with the risk and improves prediction of incident PD, and whether the risk score is associated with basic activities of daily living (BADL) in healthy individuals. METHODS: Within the population-based Rotterdam Study, we genotyped 26 independent risk variants for PD and constructed a genetic risk score in 7167 participants who were free of parkinsonism and dementia at baseline (1990 or 2000). Participants were followed for a maximum of twenty years for the onset of parkinsonism, dementia or death until January 1, 2011 (median follow-up 12.1 years). We studied the relationship between the genetic risk score and incident PD with adjustment for age, sex, smoking and parental history. In an independent sample of 2997 persons free of parkinsonism and dementia, we studied whether the PD risk score was associated with impaired BADL. RESULTS: During follow-up (median 12.1 years), 99 persons were diagnosed with incident PD. The genetic risk score was associated with incident PD (hazard ratio per standard deviation risk 1.25 [95% confidence interval = 1.02; 1.55]), but did not substantially improve prediction (change in C-statistic 0.687 [0.628; 0.745] to 0.698 [0.635; 0.760], ΔC = 0.011 [-0.011; 0.033]). The genetic risk score was associated with a higher probability of any impairment in BADL (odds ratio = 1.11 [1.00; 1.23]). CONCLUSION: Genetic variants for PD are associated with the risk of incident PD in the general population and with impairment in daily functioning in individuals without clinical parkinsonism, but do not improve the clinical prediction of PD. However, we were probably underpowered to detect a small improvement in PD prediction.

6 Article Genetic risk of neurodegenerative diseases is associated with mild cognitive impairment and conversion to dementia. 2015

Adams, Hieab H H / de Bruijn, Renée F A G / Hofman, Albert / Uitterlinden, André G / van Duijn, Cornelia M / Vernooij, Meike W / Koudstaal, Peter J / Ikram, M Arfan. ·Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address: m.a.ikram@erasmusmc.nl. ·Alzheimers Dement · Pubmed #25916564.

ABSTRACT: INTRODUCTION: Neurodegenerative diseases are a major cause of cognitive impairment and can ultimately lead to dementia. Genome-wide association studies have uncovered many genetic variants conferring risk of neurodegenerative diseases, but their role in cognitive impairment remains unexplored. METHODS: In the prospective, population-based Rotterdam Study, 3605 nondemented persons aged ≥55 years were genotyped, screened for mild cognitive impairment (MCI) in 2002 to 2005 and underwent continuous follow-up for dementia until 2012. Weighted polygenic risk scores of genetic variants for Alzheimer's disease (AD), Parkinson's disease (PD), and the frontotemporal lobar degeneration/amyotrophic lateral sclerosis disease spectrum (FTLD/ALS) were constructed and investigated for association with MCI and the subsequent conversion to dementia. RESULTS: In total, 360 (10.0%) persons had MCI, of whom 147 (4.1%) were amnestic and 213 (5.9%) nonamnestic. The AD risk score was associated with both MCI subtypes (odds ratio for all MCI 1.15 [95% CI, 1.03-1.28]), whereas PD and FTLD/ALS risk scores were associated only with nonamnestic MCI (odds ratios 1.15 [1.00-1.32] and 1.19 [1.03-1.37], respectively). The AD risk score, but not PD and FTLD/ALS risk scores, was associated with an increased risk of dementia (hazard ratio 1.55 [1.37-1.77]). DISCUSSION: Genetic evidence supports the view that multiple neurodegenerative pathways lead to MCI and that the subsequent conversion to dementia, primarily of the AD subtype, is mainly due to the AD pathway(s).

7 Article Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. 2012

Amin, N / Byrne, E / Johnson, J / Chenevix-Trench, G / Walter, S / Nolte, I M / Anonymous480704 / Vink, J M / Rawal, R / Mangino, M / Teumer, A / Keers, J C / Verwoert, G / Baumeister, S / Biffar, R / Petersmann, A / Dahmen, N / Doering, A / Isaacs, A / Broer, L / Wray, N R / Montgomery, G W / Levy, D / Psaty, B M / Gudnason, V / Chakravarti, A / Sulem, P / Gudbjartsson, D F / Kiemeney, L A / Thorsteinsdottir, U / Stefansson, K / van Rooij, F J A / Aulchenko, Y S / Hottenga, J J / Rivadeneira, F R / Hofman, A / Uitterlinden, A G / Hammond, C J / Shin, S-Y / Ikram, A / Witteman, J C M / Janssens, A C J W / Snieder, H / Tiemeier, H / Wolfenbuttel, B H R / Oostra, B A / Heath, A C / Wichmann, E / Spector, T D / Grabe, H J / Boomsma, D I / Martin, N G / van Duijn, C M. ·Unit of Genetic Epidemiology, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. ·Mol Psychiatry · Pubmed #21876539.

ABSTRACT: Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).

8 Article Genome-wide association study confirms extant PD risk loci among the Dutch. 2011

Simón-Sánchez, Javier / van Hilten, Jacobus J / van de Warrenburg, Bart / Post, Bart / Berendse, Henk W / Arepalli, Sampath / Hernandez, Dena G / de Bie, Rob M A / Velseboer, Daan / Scheffer, Hans / Bloem, Bas / van Dijk, Karin D / Rivadeneira, Fernando / Hofman, Albert / Uitterlinden, André G / Rizzu, Patrizia / Bochdanovits, Zoltan / Singleton, Andrew B / Heutink, Peter. ·Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, The Netherlands. j.simonsanchez@vumc.nl ·Eur J Hum Genet · Pubmed #21248740.

ABSTRACT: In view of the population-specific heterogeneity in reported genetic risk factors for Parkinson's disease (PD), we conducted a genome-wide association study (GWAS) in a large sample of PD cases and controls from the Netherlands. After quality control (QC), a total of 514,799 SNPs genotyped in 772 PD cases and 2024 controls were included in our analyses. Direct replication of SNPs within SNCA and BST1 confirmed these two genes to be associated with PD in the Netherlands (SNCA, rs2736990: P = 1.63 × 10(-5), OR = 1.325 and BST1, rs12502586: P = 1.63 × 10(-3), OR = 1.337). Within SNCA, two independent signals in two different linkage disequilibrium (LD) blocks in the 3' and 5' ends of the gene were detected. Besides, post-hoc analysis confirmed GAK/DGKQ, HLA and MAPT as PD risk loci among the Dutch (GAK/DGKQ, rs2242235: P = 1.22 × 10(-4), OR = 1.51; HLA, rs4248166: P = 4.39 × 10(-5), OR = 1.36; and MAPT, rs3785880: P = 1.9 × 10(-3), OR = 1.19).

9 Article OCT1 polymorphism is associated with response and survival time in anti-Parkinsonian drug users. 2011

Becker, Matthijs L / Visser, Loes E / van Schaik, Ron H N / Hofman, Albert / Uitterlinden, André G / Stricker, Bruno H Ch. ·Department of Epidemiology, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. ·Neurogenetics · Pubmed #20680652.

ABSTRACT: Substrates for the Organic Cation Transporter 1, encoded by the SLC22A1 gene, are metformin, amantadine, pramipexole, and, possibly, levodopa. Recently, we identified that the rs622342 A > C polymorphism is associated with the HbA1c lowering effect in metformin users. In the Rotterdam Study, we associated this polymorphism with higher prescribed doses of all anti-Parkinsonian drugs. Between the first and fifth prescriptions for levodopa, for each minor rs622342 C allele, the prescribed doses were 0.34 defined daily dose higher (95% CI 0.064, 0.62; p=0.017). The mortality ratio after start of levodopa therapy was 1.47 times higher (95% CI 1.01, 2.13; p=0.045).

10 Minor Association of heat shock proteins with Parkinson's disease. 2011

Broer, Linda / Koudstaal, Peter J / Amin, Najaf / Rivadeneira, Fernando / Uitterlinden, Andre G / Hofman, Albert / Oostra, Ben A / Breteler, Monique M B / Ikram, M Arfan / van Duijn, Cornelia M. · ·Eur J Epidemiol · Pubmed #22120601.

ABSTRACT: -- No abstract --