Meta-analysis of the DRD5 VNTR in persistent ADHD

Marieke Klein; Stefanie Berger; Martine Hoogman; Janneke Dammers; Remco Makkinje; Angelien J G A M Heister; Tessel E Galesloot; Lambertus A L M Kiemeney; Heike Weber; Sarah Kittel-Schneider; Klaus-Peter Lesch; Andreas Reif; Marta Ribase S; Josep Antoni Ramos-Quiroga; Bru Cormand; Tetyana Zayats; Tor-Arne Hegvik; Kaya K Jacobsen; Stefan Johansson; Jan Haavik; Nina R Mota; Claiton H D Bau; Eugenio H Grevet; Alysa Doyle; Stephen V Faraone; Alejandro Arias-Va Squez; Barbara Franke

doi:10.1016/j.euroneuro.2016.06.012

Meta-analysis of the DRD5 VNTR in persistent ADHD

Eur Neuropsychopharmacol. 2016 Sep;26(9):1527-1532. doi: 10.1016/j.euroneuro.2016.06.012. Epub 2016 Jul 29.

Authors

Marieke Klein¹, Stefanie Berger², Martine Hoogman¹, Janneke Dammers¹, Remco Makkinje¹, Angelien J G A M Heister¹, Tessel E Galesloot³, Lambertus A L M Kiemeney³, Heike Weber⁴, Sarah Kittel-Schneider⁵, Klaus-Peter Lesch⁶, Andreas Reif⁵, Marta Ribase S⁷, Josep Antoni Ramos-Quiroga⁷, Bru Cormand⁸, Tetyana Zayats⁹, Tor-Arne Hegvik¹⁰, Kaya K Jacobsen¹⁰, Stefan Johansson¹¹, Jan Haavik¹², Nina R Mota¹³, Claiton H D Bau¹³, Eugenio H Grevet¹⁴, Alysa Doyle¹⁵, Stephen V Faraone¹⁶, Alejandro Arias-Va Squez¹⁷, Barbara Franke¹⁸

Affiliations

¹ Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics, Nijmegen, The Netherlands.
² Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics, Nijmegen, The Netherlands; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
³ Radboud university medical center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
⁴ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany; Department of Psychiatry, Psychosomatics and Psychotherapy, IZKF Würzburg, University Hospital of Würzburg, Würzburg, Germany.
⁵ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
⁶ ADHD Clinical Research Unit, Division of Molecular Psychiatry, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
⁷ Biomedical Network Research Center on Mental Health (CIBERSAM), Institute of Salud Carlos III, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; Department of Psychiatry, University Hospital Vall d׳Hebron, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; Psychiatric Genetics Unit, University Hospital, Vall d׳Hebron, Barcelona, Catalonia, Spain.
⁸ Department of Genetics, Faculty of Biology, University of Barcelona, Barcelona, Catalonia, Spain; Institute of Biomedicine, University of Barcelona (IBUB), Barcelona, Catalonia, Spain; Instituto de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Spain.
⁹ K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.
¹⁰ K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
¹¹ Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Clinical Science, University of Bergen, Bergen, Norway.
¹² K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway; Department of Psychiatry, Haukeland University Hospital, Bergen, Norway.
¹³ Department of Genetics, Institute of Bioscience, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; ADHD Outpatient Program-Adult Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
¹⁴ ADHD Outpatient Program-Adult Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Department of Psychiatry, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
¹⁵ Department of Psychiatry and Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research at the Broad Institute, Cambridge, MA, USA.
¹⁶ K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Clinical Science, University of Bergen, Bergen, Norway; Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
¹⁷ Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics, Nijmegen, The Netherlands; Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, Nijmegen, The Netherlands; Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Nijmegen, The Netherlands.
¹⁸ Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics, Nijmegen, The Netherlands; Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, Nijmegen, The Netherlands. Electronic address: Barbara.franke@radboudumc.nl.

PMID: 27480019
DOI: 10.1016/j.euroneuro.2016.06.012

Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neuropsychiatric disorder with a complex genetic background. DRD5, the gene encoding the dopamine receptor D5, was recently confirmed as a candidate gene for ADHD in children through meta-analysis. In this study, we aimed at studying the association of the ADHD-associated variable number tandem repeat (VNTR) polymorphism upstream of DRD5 with adult ADHD. We compiled data from six sites of the International Multicentre persistent ADHD CollaboraTion (IMpACT) and reached N=6979 (3344 cases and 3635 healthy participants), the largest sample investigated so far. We tested the association of the common DRD5 alleles with categorically defined ADHD and with inattentive and hyperactive/impulsive symptom counts. Our findings provide evidence that none of the common DRD5 alleles are associated with ADHD risk or ADHD symptom counts in adults.

Keywords: Attention-Deficit/Hyperactivity Disorder; Candidate gene; DRD5; Meta-analysis.

Publication types

Meta-Analysis
Multicenter Study

MeSH terms

Attention Deficit Disorder with Hyperactivity / genetics*
Genetic Predisposition to Disease
Humans
Minisatellite Repeats*
Receptors, Dopamine D5 / genetics*

Substances

DRD5 protein, human
Receptors, Dopamine D5