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

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 156B; no. 5; pp. 600 - 612
• Main Authors: Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miquel, Bayés, Mònica, Bosch, Rosa, Fernàndez-Castillo, Noelia, Brunso, Lucas, Jacobsen, Kaya K., Landaas, Elisabeth T., Lundervold, Astri J., Gross-Lesch, Silke, Kreiker, Susanne, Jacob, Christian P., Lesch, Klaus-Peter, Buitelaar, Jan K., Hoogman, Martine, Kiemeney, Lambertus A.L.M., Kooij, J.J. Sandra, Mick, Eric, Asherson, Phil, Faraone, Stephen V., Franke, Barbara, Reif, Andreas, Johansson, Stefan, Haavik, Jan, Ramos-Quiroga, Josep Antoni, Cormand, Bru
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2011; Wiley-Liss
• Subjects: 3' Untranslated regions; Adult; Attention Deficit Disorder with Hyperactivity - genetics; Attention deficit hyperactivity disorder; Biological and medical sciences; case-control association study; Case-Control Studies; Children; Cognition; Data processing; Dopamine; Dopamine D4 receptors; Dopamine Plasma Membrane Transport Proteins - genetics; Dopamine transporter; Emotions; Epistasis; Europe; European Continental Ancestry Group - genetics; Exons; Female; Gene polymorphism; Genetic Testing; Haplotypes; Humans; Male; Medical genetics; Medical sciences; Middle Aged; Minisatellite Repeats; Motor task performance; neurotransmission; Polymorphism, Genetic; Promoters; psychiatric genetics; Receptors, Dopamine D4 - genetics; Reinforcement; Remission; Reviews; Risk Factors; Europe; Human; attention-deficit hyperactivity disorder; Dopamine; psychiatric genetics; Interaction; Case control study; Catecholamine; European; Metaanalysis; Association; Risk factor; case—control association study; Neurotransmitter; Adult; Genetics; Population; Attention disorder with hyperactivity; Neurotransmission
• ISSN: 1552-4841; 1552-485X; 1552-485X
• DOI: 10.1002/ajmg.b.31202

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.