title: An international multicenter association study of the serotonin transporter gene in persistent ADHD.
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.
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: E T
authors.initials: ET
authors.lastname: Landaas
authors.forename: S
authors.initials: S
authors.lastname: Johansson
authors.forename: K K
authors.initials: KK
authors.lastname: Jacobsen
authors.forename: M
authors.initials: M
authors.lastname: Ribasés
authors.forename: R
authors.initials: R
authors.lastname: Bosch
authors.forename: C
authors.initials: C
authors.lastname: Sánchez-Mora
authors.forename: C P
authors.initials: CP
authors.lastname: Jacob
authors.forename: A
authors.initials: A
authors.lastname: Boreatti-Hümmer
authors.forename: S
authors.initials: S
authors.lastname: Kreiker
authors.forename: K-P
authors.initials: KP
authors.lastname: Lesch
authors.forename: L A
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: J J S
authors.initials: JJ
authors.lastname: Kooij
authors.forename: C
authors.initials: C
authors.lastname: Kan
authors.forename: J K
authors.initials: JK
authors.lastname: Buitelaar
authors.forename: S V
authors.initials: SV
authors.lastname: Faraone
authors.forename: A
authors.initials: A
authors.lastname: Halmøy
authors.forename: J A
authors.initials: JA
authors.lastname: Ramos-Quiroga
authors.forename: B
authors.initials: B
authors.lastname: Cormand
authors.forename: A
authors.initials: A
authors.lastname: Reif
authors.forename: B
authors.initials: B
authors.lastname: Franke
authors.forename: E
authors.initials: E
authors.lastname: Mick
authors.forename: P M
authors.initials: PM
authors.lastname: Knappskog
authors.forename: J
authors.initials: J
authors.lastname: Haavik
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001008:Anxiety Disorders / Q000150:complications; D001289:Attention Deficit Disorder with Hyperactivity / Q000145:classification / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D003866:Depressive Disorder / Q000150:complications; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D008297:Male; D009426:Netherlands; D009664:Norway; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012737:Sex Factors; D013030:Spain; D014481:United States; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins