Conflict of interest: Netherlands: In the past 3 years, Jan K. Buitelaar has been a consultant to/member of advisory board of and/or speaker for Janssen Cilag BV, Eli Lilly, Bristol-Myer Squibb, Organon/Shering Plough, UCB, Shire, Medice, and Servier. He is not an employee of any of these companies. He is not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents or royalties. Sandra Kooij has received research grants from Janssen BV en Shire, and is on the speaker's bureau of Janssen and Eli Lilly. Martine Hoogman, Lambertus Kiemeney, and Barbara Franke declare no conflicts of interest. Norway: Jan Haavik has been a consultant for Janssen Cilag and Novartis. Authors from Germany and Spain declare no conflicts of interest.
Article first published online: 18 MAY 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 156, Issue 5, pages 600–612, July 2011
How to Cite
Sánchez-Mora, C., Ribasés, M., Casas, M., Bayés, M., Bosch, R., Fernàndez-Castillo, N., Brunso, L., Jacobsen, K. K., Landaas, E. T., Lundervold, A. J., Gross-Lesch, S., Kreiker, S., Jacob, C. P., Lesch, K.-P., Buitelaar, J. K., Hoogman, M., Kiemeney, L. A.L.M., Kooij, J.J. S., Mick, E., Asherson, P., Faraone, S. V., Franke, B., Reif, A., Johansson, S., Haavik, J., Ramos-Quiroga, J. A. and Cormand, B. (2011), Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta-analysis in four European populations. Am. J. Med. Genet., 156: 600–612. doi: 10.1002/ajmg.b.31202
Barbara Franke, Andreas Reif, Stefan Johansson, Jan Haavik, Josep Antoni Ramos-Quiroga, and Bru Cormand contributed equally to this study.
How to cite this article: Sánchez-Mora C, Ribasés M, Casas M, Bayés M, Bosch R, Fernàndez-Castillo N, Brunso L, Jacobsen KK, Landaas ET, Lundervold AJ, Gross-Lesch S, Kreiker S, Jacob CP, Lesch K-P, Buitelaar JK, Hoogman M, Kiemeney LALM, Kooij JJS, Mick E, Asherson P, Faraone SV, Franke B, Reif A, Johansson S, Haavik J, Ramos-Quiroga JA, Cormand B. 2011. Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta-analysis in four European populations. Am J Med Genet Part B 156:600–612.
- Issue published online: 10 JUN 2011
- Article first published online: 18 MAY 2011
- Manuscript Accepted: 25 APR 2011
- Manuscript Received: 24 NOV 2010
- “Instituto de Salud Carlos III-FIS,” Spain. Grant Numbers: PI040524 PI041267, PI080519
- “Fundació La Marató de TV3”. Grant Number: 092330/31
- “Agència de Gestió d'Ajuts Univeristaris i de Recerca-AGAUR”. Grant Number: 2009SGR-00971
- Obra Social - Fundació “La Caixa”. Grant Number: 2007-2010
- Subdirecció General de Drogodependències, Departament de Salut, and Pla Director de Salut Mental i Addiccions, Catalonia Government (Generalitat de Catalunya)
- Hersenstichting Nederland (Fonds Psychische Gezondheid)
- Research Council of Norway
- Western Norway Regional Health Authority
- The National Research Network for ADHD
- The University of Bergen
- DFG. Grant Numbers: RE1632/1-5, KFO 125 SFB TRR 58/A1,5, Z02, GRK 1156
- GK Emotions
- BMBF. Grant Number: 01GV0605
- EC. Grant Number: NEWMOOD LSHM-CT-2003-503474
- attention-deficit hyperactivity disorder;
- case–control association study;
- psychiatric genetics
Attention-deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting about 4–8% of children. ADHD persists into adulthood in around 65% of cases, either as the full condition or in partial remission with persistence of symptoms. Pharmacological, animal and molecular genetic studies support a role for genes of the dopaminergic system in ADHD due to its essential role in motor control, cognition, emotion, and reward. Based on these data, we analyzed two functional polymorphisms within the DRD4 gene (120 bp duplication in the promoter and 48 bp VNTR in exon 3) in a clinical sample of 1,608 adult ADHD patients and 2,352 controls of Caucasian origin from four European countries that had been recruited in the context of the International Multicentre persistent ADHD CollaboraTion (IMpACT). Single-marker analysis of the two polymorphisms did not reveal association with ADHD. In contrast, multiple-marker meta-analysis showed a nominal association (P = 0.02) of the L-4R haplotype (dup120bp-48bpVNTR) with adulthood ADHD, especially with the combined clinical subtype. Since we previously described association between adulthood ADHD and the dopamine transporter SLC6A3 9R-6R haplotype (3′UTR VNTR-intron 8 VNTR) in the same dataset, we further tested for gene × gene interaction between DRD4 and SLC6A3. However, we detected no epistatic effects but our results rather suggest additive effects of the DRD4 risk haplotype and the SLC6A3 gene. © 2011 Wiley-Liss, Inc.