An international multicenter association study of the serotonin transporter gene in persistent ADHD.
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.
Landaas
E T
ET
Department of Biomedicine, University of Bergen, Bergen, Norway.
Johansson
S
S
Jacobsen
K K
KK
Ribasés
M
M
Bosch
R
R
Sánchez-Mora
C
C
Jacob
C P
CP
Boreatti-Hümmer
A
A
Kreiker
S
S
Lesch
K-P
KP
Kiemeney
L A
LA
Kooij
J J S
JJ
Kan
C
C
Buitelaar
J K
JK
Faraone
S V
SV
Halmøy
A
A
Ramos-Quiroga
J A
JA
Cormand
B
B
Reif
A
A
Franke
B
B
Mick
E
E
Knappskog
P M
PM
Haavik
J
J
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
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins