Candidate gene studies of ADHD: a meta-analytic review

• Published in: Human genetics Vol. 126; no. 1; pp. 51 - 90
• Main Authors: Gizer, Ian R., Ficks, Courtney, Waldman, Irwin D.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.07.2009; Springer; Springer Nature B.V
• Subjects: Alleles; Attention Deficit Disorder with Hyperactivity - genetics; Attention-deficit hyperactivity disorder; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; Child; Development and progression; Dopamine beta-Hydroxylase - genetics; Dopamine Plasma Membrane Transport Proteins - genetics; Dopamine receptors; Etiology; Gene Function; Genes; Genetic Markers; Genetic research; Human Genetics; Humans; Hyperactivity; Metabolic Diseases; Molecular Medicine; Monoamine oxidase; Monoamine Oxidase - genetics; Polymorphism, Genetic; Quantitative genetics; Receptor, Serotonin, 5-HT1B - genetics; Receptor, Serotonin, 5-HT2A - genetics; Receptors, Adrenergic, alpha-2 - genetics; Receptors, Dopamine D4 - genetics; Receptors, Dopamine D5 - genetics; Review Article; Risk factors; Synaptosomal-Associated Protein 25 - genetics; Tryptophan Hydroxylase - genetics; United States > US
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-009-0694-x

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.