The genetics of attention deficit hyperactivity disorder.
Attention deficit hyperactivity disorder (ADHD) is a highly heritable, disruptive, childhood-onset condition, the aetiology and pathogenesis of which is poorly understood. There have been relatively few genome-wide linkage studies, and no chromosomal region has yet been unequivocally implicated. In contrast, evidence from pharmacological, neuroimaging and animal studies has suggested the involvement of specific neurotransmitter systems, notably dopaminergic pathways, in ADHD and these aetiological clues have inspired a fruitful application of the candidate gene association approach. Meta-analyses or pooled data analyses have supported association between ADHD and polymorphisms in DRD4, DRD5 and SLC6A3 which encode dopamine D4 and D5 receptors and the dopamine transporter, respectively. A weaker, but nevertheless replicated, body of evidence also supports associations with SNAP-25 (synaptosomal-associated protein, 25 kDa) and SLC6A4 (serotonin transporter). There is increasing research interest in gene-phenotype links, clinical phenotypic markers of heterogeneity and gene--environment interaction, which are likely to be important in the next generation of genetic studies.
Thapar
Anita
A
Department of Psychological Medicine, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK thapar@cardiff.ac.uk
O'Donovan
Michael
M
Owen
Michael J
MJ
D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D004777:Environment; D006801:Humans; D015201:Meta-Analysis as Topic; D008954:Models, Biological; D050638:Receptors, Dopamine D4 / Q000235:genetics; D050641:Receptors, Dopamine D5 / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics*
C493599:DRD4 protein, human; C493605:DRD5 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; C494208:SNAP25 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050825:Synaptosomal-Associated Protein 25; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5