Common variants in the TPH1 and TPH2 regions are not associated with persistent ADHD in a combined sample of 1,636 adult cases and 1,923 controls from four European populations†
Corresponding Author
Stefan Johansson
Department of Biomedicine, University of Bergen, Bergen, Norway
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
Department of Biomedicine, University of Bergen, 5009 Bergen, Norway.Search for more papers by this authorAnne Halmøy
Department of Biomedicine, University of Bergen, Bergen, Norway
Search for more papers by this authorThegna Mavroconstanti
Department of Biomedicine, University of Bergen, Bergen, Norway
Search for more papers by this authorKaya K. Jacobsen
Department of Biomedicine, University of Bergen, Bergen, Norway
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorElisabeth T. Landaas
Department of Biomedicine, University of Bergen, Bergen, Norway
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorAndreas Reif
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
Search for more papers by this authorChristian Jacob
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
Search for more papers by this authorAndrea Boreatti-Hümmer
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
Search for more papers by this authorSusanne Kreiker
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
Department of Child and Adolescent Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
Search for more papers by this authorKlaus-Peter Lesch
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
Search for more papers by this authorCornelis C. Kan
Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorJ.J. Sandra Kooij
Parnassia, Psycho-Medical Centre, The Hague, The Netherlands
Search for more papers by this authorLambertus A. Kiemeney
Department of Epidemiology & Biostatistics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Participating as representative of the Nijmegen Biomedical Study.
Search for more papers by this authorJan K. Buitelaar
Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorBarbara Franke
Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorMarta Ribasés
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
Psychiatric Genetics Unit, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
Search for more papers by this authorRosa Bosch
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
Search for more papers by this authorMònica Bayés
Genes and Disease Program, Center for Genomic Regulation (CRG-UPF), Barcelona, Catalonia, Spain
CIBER Epidemiología y Salud Pública, Barcelona, Catalonia, Spain
Centro Nacional de Genotipado (CeGen), Barcelona, Catalonia, Spain
Search for more papers by this authorMiguel Casas
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain
Search for more papers by this authorJosep Antoni Ramos-Quiroga
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain
Search for more papers by this authorBru Cormand
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Catalonia, Spain
CIBER Enfermedades Raras, Barcelona, Catalonia, Spain
Institut de Biomedicina de la Universitat de Barcelona (IBUB), Catalonia, Spain
Search for more papers by this authorPer Knappskog
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
Medical Genetics and Molecular Medicine, Department of Clinical Medicine, University of Bergen, Bergen, Norway
Search for more papers by this authorJan Haavik
Department of Biomedicine, University of Bergen, Bergen, Norway
Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorCorresponding Author
Stefan Johansson
Department of Biomedicine, University of Bergen, Bergen, Norway
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
Department of Biomedicine, University of Bergen, 5009 Bergen, Norway.Search for more papers by this authorAnne Halmøy
Department of Biomedicine, University of Bergen, Bergen, Norway
Search for more papers by this authorThegna Mavroconstanti
Department of Biomedicine, University of Bergen, Bergen, Norway
Search for more papers by this authorKaya K. Jacobsen
Department of Biomedicine, University of Bergen, Bergen, Norway
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorElisabeth T. Landaas
Department of Biomedicine, University of Bergen, Bergen, Norway
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorAndreas Reif
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
Search for more papers by this authorChristian Jacob
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
Search for more papers by this authorAndrea Boreatti-Hümmer
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
Search for more papers by this authorSusanne Kreiker
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
Department of Child and Adolescent Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
Search for more papers by this authorKlaus-Peter Lesch
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
Search for more papers by this authorCornelis C. Kan
Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorJ.J. Sandra Kooij
Parnassia, Psycho-Medical Centre, The Hague, The Netherlands
Search for more papers by this authorLambertus A. Kiemeney
Department of Epidemiology & Biostatistics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Participating as representative of the Nijmegen Biomedical Study.
Search for more papers by this authorJan K. Buitelaar
Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorBarbara Franke
Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorMarta Ribasés
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
Psychiatric Genetics Unit, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
Search for more papers by this authorRosa Bosch
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
Search for more papers by this authorMònica Bayés
Genes and Disease Program, Center for Genomic Regulation (CRG-UPF), Barcelona, Catalonia, Spain
CIBER Epidemiología y Salud Pública, Barcelona, Catalonia, Spain
Centro Nacional de Genotipado (CeGen), Barcelona, Catalonia, Spain
Search for more papers by this authorMiguel Casas
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain
Search for more papers by this authorJosep Antoni Ramos-Quiroga
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain
Search for more papers by this authorBru Cormand
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Catalonia, Spain
CIBER Enfermedades Raras, Barcelona, Catalonia, Spain
Institut de Biomedicina de la Universitat de Barcelona (IBUB), Catalonia, Spain
Search for more papers by this authorPer Knappskog
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
Medical Genetics and Molecular Medicine, Department of Clinical Medicine, University of Bergen, Bergen, Norway
Search for more papers by this authorJan Haavik
Department of Biomedicine, University of Bergen, Bergen, Norway
Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorHow to Cite this article: Johansson S, Halmøy A, Mavroconstanti T, Jacobsen KK, Landaas ET, Reif A, Jacob C, Boreatti-Hümmer A, Kreiker S, Lesch K-P, Kan CC, Kooij JJS, Kiemeney LA, Buitelaar JK, Franke B, Ribasés M, Bosch R, Bayés M, Casas M, Ramos-Quiroga JA, Cormand B, Knappskog P, Haavik J. 2010. Common Variants in the TPH1 and TPH2 Regions Are Not Associated With Persistent ADHD in a Combined Sample of 1,636 Adult Cases and 1,923 Controls From Four European Populations. Am J Med Genet Part B 153B:1008–1015.
Abstract
The tryptophan hydroxylase 1 and 2 (TPH1 and TPH2) genes encode the rate-limiting enzymes in the serotonin biosynthesis. Genetic variants in both genes have been implicated in several psychiatric disorders. For attention-deficit/hyperactivity disorder (ADHD) in children, the results are conflicting, and little is known about their role in adult ADHD patients. We therefore first genotype-tagged all common variants within both genes in a Norwegian sample of 451 patients with a diagnosis of adult ADHD and 584 controls. Six of the single nucleotide polymorphisms (SNPs) were subsequently genotyped in three additional independent European Caucasian samples of adult ADHD cases and controls from the International Multicenter persistent ADHD Collaboration (IMpACT). None of the SNPs reached formal study-wide significance in the total meta-analysis sample of 1,636 cases and 1,923 controls, despite having a power of >80% to detect a variant conferring an OR = 1.25 at P = 0.001 level. Only the TPH1 SNP rs17794760 showed nominal significance [OR = 0.84 (0.71–1.00), P = 0.05]. In conclusion, in the single largest ADHD genetic study of TPH1 and TPH2 variants presented to date (n = 3,559 individuals), we did not find consistent evidence for a substantial effect of common genetic variants on persistent ADHD. © 2010 Wiley-Liss, Inc.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
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| AJMB_31067_sm_SuppTab1.doc65.5 KB | Supplementary Table 1 |
| AJMB_31067_sm_SuppTab2.doc66 KB | Supplementary Table 2 |
| AJMB_31067_sm_SuppTab3.doc31.5 KB | Supplementary Table 3 |
| AJMB_31067_sm_SuppFig1.tif395.5 KB | Supplementary Figure 1 |
| AJMB_31067_sm_SuppFig2.tif130.4 KB | Supplementary Figure 2 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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