TY - JOUR
T1 - Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta-analysis in four European populations
AU - Sánchez-Mora, Cristina
AU - Ribasés, Marta
AU - Casas, Miquel
AU - Bayés, M. nica
AU - Bosch, Rosa
AU - Fernàndez-Castillo, Noelia
AU - Brunso, Lucas
AU - Jacobsen, Kaya K.
AU - Landaas, Elisabeth T.
AU - Lundervold, Astri J.
AU - Gross-Lesch, Silke
AU - Kreiker, Susanne
AU - Jacob, Christian P.
AU - Lesch, Klaus-Peter
AU - Buitelaar, Jan K.
AU - Hoogman, Martine
AU - Kiemeney, Lambertus A. L. M.
AU - Kooij, J. J. Sandra
AU - Mick, Eric
AU - Asherson, Phil
AU - Faraone, Stephen V.
AU - Franke, Barbara
AU - Reif, Andreas
AU - Johansson, Stefan
AU - Haavik, Jan
AU - Ramos-Quiroga, Josep Antoni
AU - Cormand, Bru
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=79958742968&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/21595008
U2 - https://doi.org/10.1002/ajmg.b.31202
DO - https://doi.org/10.1002/ajmg.b.31202
M3 - Article
C2 - 21595008
SN - 1552-4841
VL - 156
SP - 600
EP - 612
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 5
ER -