Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta-analysis in four European populations

Cristina Sánchez-Mora, Marta Ribasés, Miquel Casas, M. nica Bayés, Rosa Bosch, Noelia Fernàndez-Castillo, Lucas Brunso, Kaya K. Jacobsen, Elisabeth T. Landaas, Astri J. Lundervold, Silke Gross-Lesch, Susanne Kreiker, Christian P. Jacob, Klaus-Peter Lesch, Jan K. Buitelaar, Martine Hoogman, Lambertus A. L. M. Kiemeney, J. J. Sandra Kooij, Eric Mick, Phil AshersonStephen V. Faraone, Barbara Franke, Andreas Reif, Stefan Johansson, Jan Haavik, Josep Antoni Ramos-Quiroga, Bru Cormand

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)


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 (120bp duplication in the promoter and 48bp 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.
Original languageEnglish
Pages (from-to)600-612
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number5
Publication statusPublished - 2011
Externally publishedYes

Cite this