Molecular genetics of attention-deficit/hyperactivity disorder.
Results of behavioral genetic and molecular genetic studies have converged to suggest that both genetic and nongenetic factors contribute to the development of attention-deficit/hyperactivity disorder (ADHD). We review this literature, with a particular emphasis on molecular genetic studies. Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD. This fact is most clearly seen in the 20 extant twin studies, which estimate the heritability of ADHD to be .76. Molecular genetic studies suggest that the genetic architecture of ADHD is complex. The few genome-wide scans conducted thus far are 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 eight genes for which the same variant has been studied in three or more case-control or family-based studies, seven show statistically significant evidence of association with ADHD on the basis of the pooled odds ratio across studies: DRD4, DRD5, DAT, DBH, 5-HTT, HTR1B, and SNAP-25.
Faraone
Stephen V
SV
Medical Genetics Research Center and Department of Psychiatry, State University of New York Upstate Medical University, Syracuse, New York 13210, USA. faraones@upstate.edu
Perlis
Roy H
RH
Doyle
Alysa E
AE
Smoller
Jordan W
JW
Goralnick
Jennifer J
JJ
Holmgren
Meredith A
MA
Sklar
Pamela
P
D000300:Adoption / Q000523:psychology; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology* / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005190:Family; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D008967:Molecular Biology; D009419:Nerve Tissue Proteins / Q000235:genetics; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D050486:Serotonin Plasma Membrane Transport Proteins; D050825:Synaptosomal-Associated Protein 25; D018433:Twin Studies as Topic
C493599:DRD4 protein, human; C493605:DRD5 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C470302:HTR1B protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D044302:Receptor, Serotonin, 5-HT1B; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; C493230:SLC6A4 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; D004299:Dopamine beta-Hydroxylase