The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.
Brookes
K
K
MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, London, UK.
Xu
X
X
Chen
W
W
Zhou
K
K
Neale
B
B
Lowe
N
N
Anney
R
R
Aneey
R
R
Franke
B
B
Gill
M
M
Ebstein
R
R
Buitelaar
J
J
Sham
P
P
Campbell
D
D
Knight
J
J
Andreou
P
P
Altink
M
M
Arnold
R
R
Boer
F
F
Buschgens
C
C
Butler
L
L
Christiansen
H
H
Feldman
L
L
Fleischman
K
K
Fliers
E
E
Howe-Forbes
R
R
Goldfarb
A
A
Heise
A
A
Gabriëls
I
I
Korn-Lubetzki
I
I
Johansson
L
L
Marco
R
R
Medad
S
S
Minderaa
R
R
Mulas
F
F
Müller
U
U
Mulligan
A
A
Rabin
K
K
Rommelse
N
N
Sethna
V
V
Sorohan
J
J
Uebel
H
H
Psychogiou
L
L
Weeks
A
A
Barrett
R
R
Craig
I
I
Banaschewski
T
T
Sonuga-Barke
E
E
Eisenberg
J
J
Kuntsi
J
J
Manor
I
I
McGuffin
P
P
Miranda
A
A
Oades
R D
RD
Plomin
R
R
Roeyers
H
H
Rothenberger
A
A
Sergeant
J
J
Steinhausen
H-C
HC
Taylor
E
E
Thompson
M
M
Faraone
S V
SV
Asherson
P
P
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008995:Monoamine Oxidase / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics; D035781:Siblings; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics; D014365:Tryptophan Hydroxylase / Q000235:genetics
D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; D008995:Monoamine Oxidase; D015513:Oncogene Proteins; D050638:Receptors, Dopamine D4; D011978:Receptors, Nicotinic; D050825:Synaptosomal-Associated Protein 25; D014365:Tryptophan Hydroxylase; C493599:DRD4 protein, human; C099763:NET1 protein, human; C493214:SLC6A3 protein, human; C494784:TPH2 protein, human