Candidate gene studies of ADHD: a meta-analytic review.
Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity disorder (ADHD). Over the past 15 years, considerable efforts have been made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating variables that could explain inconsistent results. Significant associations were identified for several candidate genes including DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25. Further, significant heterogeneity was observed for the associations between ADHD and DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender, exposure to environmental risk factors). We conclude with a discussion of these findings in relation to emerging themes relevant to future studies of the genetics of ADHD.
Gizer
Ian R
IR
Department of Genetics, University of North Carolina at Chapel Hill, 120 Mason Farm Road, Room 5015 Genetic Medicine Building CB 7264, Chapel Hill, NC 27599-7264, USA. igizer@unc.edu
Ficks
Courtney
C
Waldman
Irwin D
ID
D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D008995:Monoamine Oxidase / Q000235:genetics; D011110:Polymorphism, Genetic; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics; D050638:Receptors, Dopamine D4 / Q000235:genetics; D050641:Receptors, Dopamine D5 / Q000235:genetics; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics; D014365:Tryptophan Hydroxylase / Q000235:genetics
C547768:ADRA2A protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D018341:Receptors, Adrenergic, alpha-2; C493214:SLC6A3 protein, human; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase; D004299:Dopamine beta-Hydroxylase; D008995:Monoamine Oxidase