An international multicenter association study of the serotonin transporter gene in persistent ADHD

E. T. Landaas, S. Johansson, K. K. Jacobsen, M. Ribasés, R. Bosch, C. Sánchez-Mora, C. P. Jacob, A. Boreatti-Hümmer, S. Kreiker, K. P. Lesch, L. A. Kiemeney, J. J. S. Kooij, C. Kan, J. K. Buitelaar, S. V. Faraone, A. Halmøy, J. A. Ramos-Quiroga, B. Cormand, A. Reif, B. FrankeE. Mick, P. M. Knappskog, J. Haavik

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Abstract

Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting children and adults. It has been suggested that gene variants related to serotonin neurotransmission are associated with ADHD. We tested the functional promoter polymorphism 5-HTTLPR and seven single nucleotide polymorphisms in SLC6A4 for association with ADHD in 448 adult ADHD patients and 580 controls from Norway. Replication attempts were performed in a sample of 1454 Caucasian adult ADHD patients and 1302 controls from Germany, Spain, the Netherlands and USA, and a meta-analysis was performed also including a previously published adult ADHD study. We found an association between ADHD and rs140700 [odds ratio (OR) = 0.67; P = 0.01] and the short (S) allele of the 5-HTTLPR (OR = 1.19; P = 0.06) in the Norwegian sample. Analysis of a possible gender effect suggested that the association might be restricted to females (rs140700: OR = 0.45; P = 0.00084). However, the meta-analysis of 1894 cases and 1878 controls could not confirm the association for rs140700 [OR = 0.85, 95% confidence interval (CI) = 0.67-1.09; P = 0.20]. For 5-HTTLPR, five of six samples showed a slight overrepresentation of the S allele in patients, but meta-analysis refuted a strong effect (OR = 1.10, 95% CI = 1.00-1.21; P = 0.06). Neither marker showed any evidence of differential effects for ADHD subtype, gender or symptoms of depression/anxiety. In conclusion, our results do not support a major role for SLC6A4 common variants in persistent ADHD, although a modest effect of the 5-HTTLPR and a role for rare variants cannot be excluded. © 2010 Blackwell Publishing Ltd/International Behavioural and Neural Genetics Society.
Original languageEnglish
Pages (from-to)449-458
JournalGenes, brain, and behavior
Volume9
Issue number5
DOIs
Publication statusPublished - 2010
Externally publishedYes

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