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No genetic association between attention-deficit/hyperactivity disorder (ADHD) and Parkinson’s disease in nine ADHD candidate SNPs

  • Julia M. GeisslerEmail author
  • International Parkinson Disease Genomics Consortium members
  • Marcel Romanos
  • Manfred Gerlach
  • Daniela Berg
  • Claudia Schulte
Original Article

Abstract

Attention-deficit/hyperactivity disorder (ADHD) and Parkinson’s disease (PD) involve pathological changes in brain structures such as the basal ganglia, which are essential for the control of motor and cognitive behavior and impulsivity. The cause of ADHD and PD remains unknown, but there is increasing evidence that both seem to result from a complicated interplay of genetic and environmental factors affecting numerous cellular processes and brain regions. To explore the possibility of common genetic pathways within the respective pathophysiologies, nine ADHD candidate single nucleotide polymorphisms (SNPs) in seven genes were tested for association with PD in 5333 cases and 12,019 healthy controls: one variant, respectively, in the genes coding for synaptosomal-associated protein 25 k (SNAP25), the dopamine (DA) transporter (SLC6A3; DAT1), DA receptor D4 (DRD4), serotonin receptor 1B (HTR1B), tryptophan hydroxylase 2 (TPH2), the norepinephrine transporter SLC6A2 and three SNPs in cadherin 13 (CDH13). Information was extracted from a recent meta-analysis of five genome-wide association studies, in which 7,689,524 SNPs in European samples were successfully imputed. No significant association was observed after correction for multiple testing. Therefore, it is reasonable to conclude that candidate variants implicated in the pathogenesis of ADHD do not play a substantial role in PD.

Keywords

ADHD Parkinson’s disease GWAS SNPs CDH13 Dopamine transporter 

Notes

Acknowledgements

International Parkinson Disease Genomics Consortium members: Mike Nalls (Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA), Vincent Plagnol (UCL Genetics Institute, London, UK), Dena G Hernandez (Laboratory of Neurogenetics, National Institute on Aging; and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK), Manu Sharma (Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany), Una-Marie Sheerin (Department of Molecular Neuroscience, UCL Institute of Neurology), Mohamad Saad (INSERM U563, CPTP, Toulouse, France; and Paul Sabatier University, Toulouse, France), Javier Simón-Sánchez (Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, Netherlands), Claudia Schulte (Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research), Suzanne Lesage (INSERM, UMR_S975 [formerly UMR_S679], Paris, France; Université Pierre et Marie Curie-Paris, Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière, Paris, France; and CNRS, Paris, France), Sigurlaug Sveinbjörnsdóttir (Department of Neurology, Landspítali University Hospital, Reykjavík, Iceland; Department of Neurology, MEHT Broomfield Hospital, Chelmsford, Essex, UK; and Queen Mary College, University of London, London, UK), Sampath Arepalli (Laboratory of Neurogenetics, National Institute on Aging), Roger Barker (Department of Neurology, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK), Yoav Ben-Shlomo (School of Social and Community Medicine, University of Bristol), Henk W Berendse (Department of Neurology and Alzheimer Center, VU University Medical Center), Daniela Berg (Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research), Kailash Bhatia (Department of Motor Neuroscience, UCL Institute of Neurology), Rob M A de Bie (Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands), Alessandro Biffi (Center for Human Genetic Research and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA), Bas Bloem (Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands), Zoltan Bochdanovits (Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre), Michael Bonin (Department of Medical Genetics, Institute of Human Genetics, University of Tübingen, Tübingen, Germany), Jose M Bras (Department of Molecular Neuroscience, UCL Institute of Neurology), Kathrin Brockmann (Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research), Janet Brooks (Laboratory of Neurogenetics, National Institute on Aging), David J Burn (Newcastle University Clinical Ageing Research Unit, Campus for Ageing and Vitality, Newcastle upon Tyne, UK), Gavin Charlesworth (Department of Molecular Neuroscience, UCL Institute of Neurology), Honglei Chen (Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, NC, USA), Patrick F Chinnery (Neurology M4104, The Medical School, Framlington Place, Newcastle upon Tyne, UK), Sean Chong (Laboratory of Neurogenetics, National Institute on Aging), Carl E Clarke (School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK; and Department of Neurology, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK), Mark R Cookson (Laboratory of Neurogenetics, National Institute on Aging), J Mark Cooper (Department of Clinical Neurosciences, UCL Institute of Neurology), Jean Christophe Corvol (INSERM, UMR_S975; Université Pierre et Marie Curie-Paris; CNRS; and INSERM CIC-9503, Hôpital Pitié-Salpêtrière, Paris, France), Carl Counsell (University of Aberdeen, Division of Applied Health Sciences, Population Health Section, Aberdeen, UK), Philippe Damier (CHU Nantes, CIC0004, Service de Neurologie, Nantes, France), Jean-François Dartigues (INSERM U897, Université Victor Segalen, Bordeaux, France), Panos Deloukas (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK), Günther Deuschl (Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Christian-Albrechts-Universität Kiel, Kiel, Germany), David T Dexter (Parkinson’s Disease Research Group, Faculty of Medicine, Imperial College London, London, UK), Karin D van Dijk (Department of Neurology and Alzheimer Center, VU University Medical Center), Allissa Dillman (Laboratory of Neurogenetics, National Institute on Aging), Frank Durif (Service de Neurologie, Hôpital Gabriel Montpied, Clermont-Ferrand, France), Alexandra Dürr (INSERM, UMR_S975; Université Pierre et Marie Curie-Paris; CNRS; and AP-HP, Pitié-Salpêtrière Hospital), Sarah Edkins (Wellcome Trust Sanger Institute), Jonathan R Evans (Cambridge Centre for Brain Repair, Cambridge, UK), Thomas Foltynie (UCL Institute of Neurology), Jianjun Gao (Epidemiology Branch, National Institute of Environmental Health Sciences), Michelle Gardner (Department of Molecular Neuroscience, UCL Institute of Neurology), J Raphael Gibbs (Laboratory of Neurogenetics, National Institute on Aging; and Department of Molecular Neuroscience, UCL Institute of Neurology), Alison Goate (Department of Psychiatry, Department of Neurology, Washington University School of Medicine, MI, USA), Emma Gray (Wellcome Trust Sanger Institute), Rita Guerreiro (Department of Molecular Neuroscience, UCL Institute of Neurology), Ómar Gústafsson (deCODE genetics and Department of Psychiatry, Oslo University Hospital, N-0407 Oslo, Norway), Clare Harris (University of Aberdeen), Jacobus J van Hilten (Department of Neurology, Leiden University Medical Center, Leiden, Netherlands), Albert Hofman (Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands), Albert Hollenbeck (AARP, Washington DC, USA), Janice Holton (Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology), Michele Hu (Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK), Xuemei Huang (Departments of Neurology, Radiology, Neurosurgery, Pharmacology, Kinesiology, and Bioengineering, Pennsylvania State University–Milton S Hershey Medical Center, Hershey, PA, USA), Heiko Huber (Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research), Gavin Hudson (Neurology M4104, The Medical School, Newcastle upon Tyne, UK), Sarah E Hunt (Wellcome Trust Sanger Institute), Johanna Huttenlocher (deCODE genetics), Thomas Illig (Institute of Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany), Pálmi V Jónsson (Department of Geriatrics, Landspítali University Hospital, Reykjavík, Iceland), Jean-Charles Lambert (INSERM U744, Lille, France; and Institut Pasteur de Lille, Université de Lille Nord, Lille, France), Cordelia Langford (Cambridge Centre for Brain Repair), Andrew Lees (Queen Square Brain Bank for Neurological Disorders), Peter Lichtner (Institute of Human Genetics, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany), Patricia Limousin (Institute of Neurology, Sobell Department, Unit of Functional Neurosurgery, London, UK), Grisel Lopez (Section on Molecular Neurogenetics, Medical Genetics Branch, NHGRI, National Institutes of Health), Delia Lorenz (Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein), Alisdair McNeill (Department of Clinical Neurosciences, UCL Institute of Neurology), Catriona Moorby (School of Clinical and Experimental Medicine, University of Birmingham), Matthew Moore (Laboratory of Neurogenetics, National Institute on Aging), Huw R Morris (MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK), Karen E Morrison (School of Clinical and Experimental Medicine, University of Birmingham; and Neurosciences Department, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK), Ese Mudanohwo (Neurogenetics Unit, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery), Sean S O’Sullivan (Queen Square Brain Bank for Neurological Disorders), Justin Pearson (MRC Centre for Neuropsychiatric Genetics and Genomics), Joel S Perlmutter (Department of Neurology, Radiology, and Neurobiology at Washington University, St Louis), Hjörvar Pétursson (deCODE genetics; and Department of Medical Genetics, Institute of Human Genetics, University of Tübingen), Pierre Pollak (Service de Neurologie, CHU de Grenoble, Grenoble, France), Bart Post (Department of Neurology, Radboud University Nijmegen Medical Centre), Simon Potter (Wellcome Trust Sanger Institute), Bernard Ravina (Translational Neurology, Biogen Idec, MA, USA), Tamas Revesz (Queen Square Brain Bank for Neurological Disorders), Olaf Riess (Department of Medical Genetics, Institute of Human Genetics, University of Tübingen), Fernando Rivadeneira (Departments of Epidemiology and Internal Medicine, Erasmus University Medical Center), Patrizia Rizzu (Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre), Mina Ryten (Department of Molecular Neuroscience, UCL Institute of Neurology), Stephen Sawcer (University of Cambridge, Department of Clinical Neurosciences, Addenbrooke’s hospital, Cambridge, UK), Anthony Schapira (Department of Clinical Neurosciences, UCL Institute of Neurology), Hans Scheffer (Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands), Karen Shaw (Queen Square Brain Bank for Neurological Disorders), Ira Shoulson (Department of Neurology, University of Rochester, Rochester, NY, USA), Ellen Sidransky (Section on Molecular Neurogenetics, Medical Genetics Branch, NHGRI), Colin Smith (Department of Pathology, University of Edinburgh, Edinburgh, UK), Chris C A Spencer (Wellcome Trust Centre for Human Genetics, Oxford, UK), Hreinn Stefánsson (deCODE genetics), Stacy Steinberg (deCODE genetics), Joanna D Stockton (School of Clinical and Experimental Medicine), Amy Strange (Wellcome Trust Centre for Human Genetics), Kevin Talbot (University of Oxford, Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK), Carlie M Tanner (Clinical Research Department, The Parkinson’s Institute and Clinical Center, Sunnyvale, CA, USA), Avazeh Tashakkori-Ghanbaria (Wellcome Trust Sanger Institute), François Tison (Service de Neurologie, Hôpital Haut-Lévêque, Pessac, France), Daniah Trabzuni (Department of Molecular Neuroscience, UCL Institute of Neurology), Bryan J Traynor (Laboratory of Neurogenetics, National Institute on Aging), André G Uitterlinden (Departments of Epidemiology and Internal Medicine, Erasmus University Medical Center), Daan Velseboer (Department of Neurology, Academic Medical Center), Marie Vidailhet (INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225), Robert Walker (Department of Pathology, University of Edinburgh), Bart van de Warrenburg (Department of Neurology, Radboud University Nijmegen Medical Centre), Mirdhu Wickremaratchi (Department of Neurology, Cardiff University, Cardiff, UK), Nigel Williams (MRC Centre for Neuropsychiatric Genetics and Genomics), Caroline H Williams-Gray (Department of Neurology, Addenbrooke’s Hospital), Sophie Winder-Rhodes (Department of Psychiatry and Medical Research Council and Wellcome Trust Behavioural and Clinical Neurosciences Institute, University of Cambridge), Kári Stefánsson (deCODE genetics), Maria Martinez (INSERM U563; and Paul Sabatier University), John Hardy (Department of Molecular Neuroscience, UCL Institute of Neurology), Peter Heutink (Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre), Alexis Brice (INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtrière Hospital). Wellcome Trust Case-Control Consortium 2 (webappendix p 13): Thomas Gasser (Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, and DZNE, German Center for Neurodegenerative Diseases), Andrew B Singleton (Laboratory of Neurogenetics, National Institute on Aging), Nicholas W Wood (UCL Genetics Institute; and Department of Molecular Neuroscience, UCL Institute of Neurology).

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standards

All studies contributing data for this publication have been approved by the local ethics committees and were performed in accordance with the 1964 Declaration of Helsinki and its subsequent amendments. Informed consent was obtained from all participants prior to their inclusion in the study.

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Copyright information

© Springer-Verlag Wien 2017

Authors and Affiliations

  1. 1.Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental HealthUniversity Hospital of WürzburgWürzburgGermany
  2. 2.Department of Neurodegeneration, Hertie-Institute of Clinical Brain ResearchUniversity of TübingenTübingenGermany
  3. 3.DZNE—German Center for Neurodegenerative DiseasesUniversity of TübingenTübingenGermany
  4. 4.Department of NeurologyChristian-Albrechts-UniversityKielGermany

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