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Meta-analysis of brain-derived neurotrophic factor p.Val66Met in adult ADHD in four European populations

Authors

  • C. Sánchez-Mora,

    1. Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
    2. Psychiatric Genetics Unit, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
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  • M. Ribasés,

    1. Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
    2. Psychiatric Genetics Unit, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
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  • J.A. Ramos-Quiroga,

    1. Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
    2. Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain
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  • M. Casas,

    1. Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
    2. Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain
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  • R. Bosch,

    1. Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
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  • A. Boreatti-Hümmer,

    1. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
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  • M. Heine,

    1. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
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  • C.P. Jacob,

    1. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
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  • K-P. Lesch,

    1. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
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  • O.B. Fasmer,

    1. Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
    2. Section of Psychiatry, Department of Clinical Medicine, University of Bergen, Bergen, Norway
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  • P.M. Knappskog,

    1. Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Haukeland, Norway
    2. Medical Genetics and Molecular Medicine, Department of Clinical Medicine, University of Bergen, Bergen, Norway
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  • J.J. Sandra Kooij,

    1. PsyQ, Psycho-Medical Programs, Program Adult ADHD, The Hague, The Netherlands
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  • C. Kan,

    1. Department of Psychiatry, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • J.K. Buitelaar,

    1. Department of Psychiatry, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • E. Mick,

    1. Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
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  • P. Asherson,

    1. MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, London, UK
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  • S.V. Faraone,

    1. Departments of Psychiatry and Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York
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  • B. Franke,

    1. Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    2. Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
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  • S. Johansson,

    1. Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Haukeland, Norway
    2. Department of Biomedicine, University of Bergen, Bergen, Norway
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  • J. Haavik,

    1. Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
    2. Department of Biomedicine, University of Bergen, Bergen, Norway
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  • A. Reif,

    1. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
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  • M. Bayés,

    1. Genes and Disease Program, Center for Genomic Regulation (CRG-UPF), Barcelona, Catalonia, Spain
    2. CIBER Epidemiología y Salud Pública, Barcelona, Catalonia, Spain
    3. Centro Nacional de Genotipado (CeGen), Barcelona, Catalonia, Spain
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  • B. Cormand

    Corresponding author
    1. Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Catalonia, Spain
    2. CIBER Enfermedades Raras, Barcelona, Catalonia, Spain
    3. Institut de Biomedicina de la Universitat de Barcelona (IBUB), Catalonia, Spain
    • Associate Professor of Genetics, Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal 645, edifici annex, 3a planta, 08028 Barcelona, Spain.

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  • B. Franke, S. Johansson, J. Haavik, A. Reif, M. Bayés, and B. Cormand contributed equally to this work as senior members of the International Multicentre Persistent ADHD CollaboraTion (IMpACT).

  • How to Cite this Article: Sánchez-Mora C, Ribasés M, Ramos-Quiroga JA, Casas M, Bosch R, Boreatti-Hümmer A, Heine M, Jacob CP, Lesch K-P, Fasmer OB, Knappskog PM, Sandra Kooij JJ, Kan C, Buitelaar JK, Mick E, Asherson P, Faraone SV, Franke B, Johansson S, Haavik J, Reif A, Bayés M, Cormand B. 2009. Meta-Analysis of Brain-Derived Neurotrophic Factor p.Val66Met in Adult ADHD in Four European Populations. Am J Med Genet Part B 153B:512–523.

Abstract

Attention-deficit hyperactivity disorder (ADHD) is a multifactorial, neurodevelopmental disorder that often persists into adolescence and adulthood and is characterized by inattention, hyperactivity and impulsiveness. Before the advent of the first genome-wide association studies in ADHD, genetic research had mainly focused on candidate genes related to the dopaminergic and serotoninergic systems, although several other genes had also been assessed. Pharmacological data, analysis of animal models and association studies suggest that Brain-Derived Neurotrophic Factor (BDNF) is also a strong candidate gene for ADHD. Several polymorphisms in BDNF have been reported and studied in psychiatric disorders but the most frequent is the p.Val66Met (rs6265G > A) single nucleotide polymorphism (SNP), with functional effects on the intracellular trafficking and secretion of the protein. To deal with the inconsistency raised among different case–control and family-based association studies regarding the p.Val66Met contribution to ADHD, we performed a meta-analysis of published as well as unpublished data from four different centers that are part of the International Multicentre Persistent ADHD CollaboraTion (IMpACT). A total of 1,445 adulthood ADHD patients and 2,247 sex-matched controls were available for the study. No association between the p.Val66Met polymorphism and ADHD was found in any of the four populations or in the pooled sample. The meta-analysis also showed that the overall gene effect for ADHD was not statistically significant when gender or comorbidity with mood disorders were considered. Despite the potential role of BDNF in ADHD, our data do not support the involvement of p.Val66Met in the pathogenesis of this neuropsychiatric disorder. © 2009 Wiley-Liss, Inc.

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