Candidate gene studies of attention-deficit/hyperactivity disorder.
A growing body of behavioral and molecular genetics literature has indicated that the development of attention-deficit/hyperactivity disorder (ADHD) may be attributed to both genetic and environmental factors. Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD. Molecular genetic studies suggest that the genetic architecture of ADHD is complex, while the handful of genome-wide scans conducted thus far is not conclusive. In contrast, the many candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder. For the 8 genes for which the same variant has been studied in 3 or more case-control or family-based studies, 7 show statistically significant evidence of association with ADHD based on pooled odds ratios across studies: the dopamine D4 receptor gene (DRD4), the dopamine D5 receptor gene (DRD5), the dopamine transporter gene (DAT), the dopamine beta-hydroxylase gene (DBH), the serotonin transporter gene (5-HTT), the serotonin receptor 1B gene (HTR1B), and the synaptosomal-associated protein 25 gene (SNAP25). Recent pharmacogenetic studies have correlated treatment nonresponse with particular gene markers, while preclinical studies have increased our understanding of gene expression paradigms and potential analogs for human trials. This literature review discusses the relevance and implications of genetic associations with ADHD for clinical practice and future research.
Faraone
Stephen V
SV
Medical Genetics Research Program and Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY 13210, USA. faraones@upstate.edu
Khan
Sajjad A
SA
D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005819:Genetic Markers; D014644:Genetic Variation; D006801:Humans; D015201:Meta-Analysis as Topic; D010597:Pharmacogenetics; D050638:Receptors, Dopamine D4 / Q000235:genetics; D050641:Receptors, Dopamine D5 / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics
D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D050825:Synaptosomal-Associated Protein 25; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D004299:Dopamine beta-Hydroxylase