Cited by 252Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorGenetic Associations and Epidemiology

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Molecular genetics of attention-deficit/hyperactivity disorder: an overview

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Banaschewski, Tobias, Becker, Katja, Scherag, Susann, Franke, Barbara, Coghill, David·2010·European Child & Adolescent Psychiatry

DOI 10.1007/s00787-010-0090-zPMC PMC2839490

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Abstract

As heritability is high in attention-deficit/hyperactivity disorder (ADHD), genetic factors must play a significant role in the development and course of this disorder. In recent years a large number of studies on different candidate genes for ADHD have been published, most have focused on genes involved in the dopaminergic neurotransmission system, such as DRD4, DRD5, DAT1/SLC6A3, DBH, DDC. Genes associated with the noradrenergic (such as NET1/SLC6A2, ADRA2A, ADRA2C) and serotonergic systems (such as 5-HTT/SLC6A4, HTR1B, HTR2A, TPH2) have also received considerable interest. Additional candidate genes related to neurotransmission and neuronal plasticity that have been studied less intensively include SNAP25, CHRNA4, NMDA, BDNF, NGF, NTF3, NTF4/5, GDNF. This review article provides an overview of these candidate gene studies, and summarizes findings from recently published genome-wide association studies (GWAS). GWAS is a relatively new tool that enables the identification of new ADHD genes in a hypothesis-free manner. Although these latter studies could be improved and need to be replicated they are starting to implicate processes like neuronal migration and cell adhesion and cell division as potentially important in the aetiology of ADHD and have suggested several new directions for future ADHD genetics studies.

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Initial Genome Scan of the NIMH Genetics Initiative Bipolar Pedigrees: Chromosomes 4, 7, 9, 18, 19, 20, and 21q
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Confirmation That a Specific Haplotype of the Dopamine Transporter Gene Is Associated With Combined-Type ADHD
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The short DRD4 repeats confer risk to attention deficit hyperactivity disorder in a family-based design and impair performance on a continuous performance test (TOVA)
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Neuropsychological functioning in stimulant-naive boys with hyperkinetic disorder
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Statistical Approaches to Complex Phenotypes: Evaluating Neuropsychological Endophenotypes for Attention-Deficit/Hyperactivity Disorder
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Genome-wide association scan of the time to onset of Attention Deficit Hyperactivity Disorder
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The IMAGE project: methodological issues for the molecular genetic analysis of ADHD.
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Association of the Cannabinoid Receptor Gene (CNR1) With ADHD and Post-Traumatic Stress Disorder
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Association of the glutamate receptor subunit gene GRIN2B with attention‐deficit/hyperactivity disorder
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Age-related changes in the association between serotonergic function and aggression in boys with ADHD
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An examination of the behavioral and neuropsychological correlates of three ADHD candidate gene polymorphisms (DRD4 7+, DBH TaqI A2, and DAT1 40 bp VNTR) in hyperactive and normal children followed to adulthood
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Further evidence for the association between attention‐deficit/hyperactivity disorder and the dopamine‐β‐hydroxylase gene
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Genome-wide linkage analysis of ADHD using high-density SNP arrays: novel loci at 5q13.1 and 14q12
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Linkage of the dopamine receptor D1 gene to attention-deficit/hyperactivity disorder
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Dopamine Transporter Genotype Conveys Familial Risk of Attention-Deficit/Hyperactivity Disorder Through Striatal Activation
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Quantitative trait locus analysis of candidate gene alleles associated with attention deficit hyperactivity disorder (ADHD) in five genes: DRD4, DAT1, DRD5, SNAP‐25, and 5HT1B
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A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population
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A functional dopamine-β-hydroxylase gene promoter polymorphism is associated with impulsive personality styles, but not with affective disorders
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Prediction of Heterogeneity in Intelligence and Adult Prognosis by Genetic Polymorphisms in the Dopamine System Among Children With Attention-Deficit/Hyperactivity Disorder
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Does parental expressed emotion moderate genetic effects in ADHD? an exploration using a genome wide association scan
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New potential leads in the biology and treatment of attention deficit-hyperactivity disorder
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DRD4 gene variants and sustained attention in attention deficit hyperactivity disorder (ADHD): Effects of associated alleles at the VNTR and −521 SNP
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Sexually dimorphic effects of four genes (COMT, SLC6A2, MAOA, SLC6A4) in genetic associations of ADHD: A preliminary study
Biederman, J., Kim, J. W., Doyle, A. E., Mick, E., Fagerness, J., Smoller, J. W., & Faraone, S. V. (2008) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30874 · Cited by 100
Association of DRD4 in children with ADHD and comorbid conduct problems
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Methylphenidate restores visual memory, but not working memory function in attention deficit-hyperkinetic disorder
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The cognitive genetics of attention deficit hyperactivity disorder (ADHD): Sustained attention as a candidate phenotype
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Establishment of genetic associations for complex diseases is independent of early study findings
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Imaging genetics in ADHD: A focus on cognitive control
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Informative phenotypes for genetic studies of psychiatric disorders
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Potassium Channels: Newly Found Players in Synaptic Plasticity
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Tph2 gene variants modulate response control processes in adult ADHD patients and healthy individuals
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Attention Deficit Hyperactivity Disorder comorbid oppositional defiant disorder and its predominately inattentive type: evidence for an association with COMT but not MAOA in a Chinese sample
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A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16
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Meta-analysis of Association Between a Catechol-O-Methyltransferase Gene Polymorphism and Attention Deficit Hyperactivity Disorder
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Refining the attention deficit hyperactivity disorder phenotype for molecular genetic studies
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Preferential Transmission of Paternal Alleles at Risk Genes in Attention-Deficit/Hyperactivity Disorder
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The norepinephrine transporter gene and attention‐deficit hyperactivity disorder
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Association and linkage of allelic variants of the dopamine transporter gene in ADHD
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The genetics of attention-deficit/hyperactivity disorder
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Association of the dopamine transporter (SLC6A3/DAT1) gene 9–6 haplotype with adult ADHD
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“[55] reported that the 9–6 haplotype rather than the 10–6 haplotype is more likely to be associated with childhood ADHD.”
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Association between alpha-2a-adrenergic receptor gene and ADHD inattentive type.
Schmitz, M., Denardin, D., Silva, T. L., Pianca, T., Román, T., Hutz, M., Faraone, S., & Rohde, L. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.035 · Cited by 77
SNPs in Dopamine D2 Receptor Gene (DRD2) and Norepinephrine Transporter Gene (NET) Are Associated with Continuous Performance Task (CPT) Phenotypes in ADHD children and their families
Kollins, S., Anastopoulos, A., Lachiewicz, A., Fitzgerald, D., Morrissey-Kane, E., Garrett, M., Keatts, S., & Ashley-Koch, A. (2008) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30876 · Cited by 75
Neuropsychological endophenotype approach to genome-wide linkage analysis identifies susceptibility loci for ADHD on 2q21.1 and 13q12.11
Rommelse, N. N. J., Arias-Vásquez, A., Altink, M. E., Buschgens, C. J. M., Fliers, E., Asherson, P., Faraone, S. V., Buitelaar, J. K., Sergeant, J. A., Oosterlaan, J., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.06.006 · Cited by 75
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Genotypic interaction between DRD4 and DAT1 loci is a high risk factor for attention‐deficit/hyperactivity disorder in Chilean families
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Absence of the 7‐repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls
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Linkage Analysis of Attention Deficit Hyperactivity Disorder
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Genetic Risk for Conduct Disorder Symptom Subtypes in an ADHD Sample: Specificity to Aggressive Symptoms
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Meta‐analysis of brain‐derived neurotrophic factor p.Val66Met in adult ADHD in four European populations
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Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a positional candidate for attention-deficit/hyperactivity disorder in the 16p13 region
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The −1021 C/T DBH polymorphism is associated with neuropsychological performance among children and adolescents with ADHD
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A review and analysis of the relationship between neuropsychological measures and DAT1 in ADHD
Rommelse, N. N. J., Altink, M. E., Vásquez, A. A., Buschgens, C. J. M., Fliers, E. A., Faraone, S. V., Buitelaar, J. K., Sergeant, J. A., Franke, B., & Oosterlaan, J. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30848 · Cited by 64
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MAOA promoter polymorphism and attention deficit hyperactivity disorder (ADHD) in indian children
Das, M., Das Bhowmik, A., Sinha, S., Chattopadhyay, A., Chaudhuri, K., Singh, M., & Mukhopadhyay, K. (2006) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30385 · Cited by 63
Association between Catechol O‐methyltransferase (COMT) haplotypes and severity of hyperactivity symptoms in Adults
Halleland, H. B., Lundervold, A. J., Halmøy, A., Haavik, J., & Johansson, S. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30831 · Cited by 63
A psycho-genetic study of associations between the symptoms of binge eating disorder and those of attention deficit (hyperactivity) disorder
Davis, C. A., Patte, K. A., Levitan, R. D., Carter, J., Kaplan, A. S., Zai, C. C. H., Reid, C., Curtis, C., & Kennedy, J. L. (2008) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2008.10.010 · Cited by 59
The future of genetics in psychology and psychiatry: microarrays, genome‐wide association, and non‐coding RNA
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Association between cannabinoid receptor gene (CNR1) and childhood attention deficit/hyperactivity disorder in Spanish male alcoholic patients
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Pooled genome-wide linkage data on 424 ADHD ASPs suggests genetic heterogeneity and a common risk locus at 5p13
Ogdie, M. N., Bakker, S., Fisher, S., Francks, C., Yang, M. H., Cantor, R., Loo, S., van der Meulen, E. M., Pearson, P. L., Buitelaar, J., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001760 · Cited by 57
Association between polymorphisms in serotonin transporter gene and attention deficit hyperactivity disorder in Chinese Han subjects
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Report from the 4th International Meeting of the Attention Deficit Hyperactivity Disorder Molecular Genetics Network
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Further evidence of association between two NET single-nucleotide polymorphisms with ADHD
Kim, J.-W., Biederman, J., McGrath, C., Doyle, A., Mick, E., Fagerness, J., Purcell, S., Smoller, J., Sklar, P., & Faraone, S. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002090 · Cited by 57
A common haplotype at the dopamine transporter gene 5′ region is associated with attention‐deficit/hyperactivity disorder
Genro, J. P., Polanczyk, G. V., Zeni, C., Salatino‐Oliveira, A., Roman, T., Rohde, L. A., & Hutz, M. H. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30863 · Cited by 56
The adrenergic receptor -A gene (ADRA2A) and neuropsychological executive functions as putative endophenotypes for childhood ADHD
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DNA pooling analysis of 21 norepinephrine transporter gene SNPs with attention deficit hyperactivity disorder: No evidence for association
Xu, X., Knight, J., Brookes, K. J., Mill, J. S., Sham, P. C., Craig, I., Taylor, E. A., & Asherson, P. J. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30160 · Cited by 55
Relationship between endophenotype and phenotype in ADHD
Rommelse, N. N. J., Altink, M. E., Martin, N. C., Buschgens, C. J. M., Faraone, S. V., Buitelaar, J. K., Sergeant, J. A., & Oosterlaan, J. (2008) · Behavioral and Brain Functions · doi:10.1186/1744-9081-4-4 · Cited by 54
No evidence of linkage or association between the norepinephrine transporter (NET) gene polymorphisms and ADHD in the Irish population
McEvoy, B., Hawi, Z., Fitzgerald, M., & Gill, M. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10416 · Cited by 52
Gene for the serotonin transporter and ADHD: No association with two functional polymorphisms
Wigg, K. G., Takhar, A., Ickowicz, A., Tannock, R., Kennedy, J. L., Pathare, T., MALONE, M. A., Schachar, R. J., & Barr, C. L. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30247 · Cited by 50
Association of ADHD with genetic variants in the 5′‐region of the dopamine transporter gene: Evidence for allelic heterogeneity
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Some ADHD polymorphisms (in genes DAT1, DRD2, DRD3, DBH, 5-HTT) in case-control study of 100 subjects 6-10 age.
Kopečková, M., Paclt, I., Petrásek, J., Pacltová, D., Malíková, M., & Zagatová, V. (2008) · PubMed · Cited by 48
A family‐based study of Indian subjects from Kolkata reveals allelic association of the serotonin transporter intron‐2 (STin2) polymorphism and attention‐deficit‐hyperactivity disorder (ADHD)
Banerjee, E., Sinha, S., Chatterjee, A., Gangopadhyay, P. K., Singh, M., & Nandagopal, K. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30296 · Cited by 48
Spatial Attentional Bias as a Marker of Genetic Risk, Symptom Severity, and Stimulant Response in ADHD
Bellgrove, M. A., Barry, E., Johnson, K. A., Cox, M., Dáibhis, A., Daly, M., Hawi, Z., Lambert, D., Fitzgerald, M., McNicholas, F., et al. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301637 · Cited by 48
Molecular genetic contribution to the developmental course of attention-deficit hyperactivity disorder
Langley, K., Fowler, T. A., Grady, D. L., Moyzis, R. K., Holmans, P. A., van den Bree, M. B. M., Owen, M. J., O’Donovan, M. C., & Thapar, A. (2009) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-008-0698-4 · Cited by 47
Possible association of the alpha‐2A adrenergic receptor gene (ADRA2A) with symptoms of attention‐deficit/hyperactivity disorder
Wang, B., Wang, Y., Zhou, R., Li, J., Qian, Q., Yang, L., Guan, L., & Faraone, S. V. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30258 · Cited by 47
Serotonin 5‐HT1B receptor gene and attention deficit hyperactivity disorder in Chinese Han subjects
Li, J., Wang, Y., Zhou, R., Zhang, H., Yang, L., Wang, B., Khan, S., & Faraone, S. V. (2004) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30075 · Cited by 46
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Association of dopamine D4 receptor (DRD4) polymorphisms with attention deficit hyperactivity disorder in Indian population
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Self-citation
Monoamine oxidase A gene polymorphism predicts adolescent outcome of attention‐deficit/hyperactivity disorder
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A Quantitative Trait Locus Analysis of Social Responsiveness in Multiplex Autism Families
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Differential association between MAOA, ADHD and neuropsychological functioning in boys and girls
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Self-citation
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A promoter polymorphism (−839 C > T) at the dopamine transporter gene is associated with attention deficit/hyperactivity disorder in Brazilian children
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Association study of promoter polymorphisms at the dopamine transporter gene in Attention Deficit Hyperactivity Disorder
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Association between tryptophan hydroxylase gene polymorphisms and attention deficit hyperactivity disorder in Chinese Han population
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Self-citation
DNA pooling analysis of ADHD and genes regulating vesicle release of neurotransmitters
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The monoamine oxidase B gene exhibits significant association to ADHD
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Evaluation of potential gene–gene interactions for attention deficit hyperactivity disorder in the Han Chinese population
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Self-citation
Association between the alpha-2C-adrenergic receptor gene and attention deficit hyperactivity disorder in a Korean sample
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Self-citation
Verbal but not performance IQ is highly correlated to externalizing behavior in boys with ADHD carrying both DRD4 and DAT1 risk genotypes
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Research works printed but not linked: 1

Wermter A-K, Laucht M, Schimmelmann B, Banaschewski T, Sonuga-Barke E, Rietschel M, Becker K From Nature versus Nurture to Nature and Nurture: Gene × Environment Interactions in Mental Disorder—a selective review

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Authors: Banaschewski, T., Becker, K., Scherag, S., Franke, B., & Coghill, D.
Affiliations: Central Institute of Mental Health (DE)
Philipps University of Marburg (DE)
Essen University Hospital (DE)
Radboud University Nijmegen (NL)
University of Dundee (GB)
Corresponding author: Banaschewski, Tobias
ORCID: Banaschewski, Tobias
Becker, Katja
Franke, Barbara
Coghill, David
Venue: European Child & Adolescent Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2010-02-10
Volume: 19
Issue: 3
Pages: 237-257
ISSN: 1018-8827 (ISSN-L)
1435-165X
DOI: 10.1007/s00787-010-0090-z
PMC: PMC2839490
OpenAlex: W2124674986
Cited by: 252
References: 201
Citations by year: 2026: 4 · 2025: 6 · 2024: 6 · 2023: 11 · 2022: 9 · 2021: 10 · 2020: 10 · 2019: 10 · 2018: 11 · 2017: 14 · 2016: 23 · 2015: 26 · 2014: 14 · 2013: 24 · 2012: 37
FWCI: 4.35
Type: journal article
Language: en
Update notices: erratum (2010-04-28)
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: European Child & Adolescent Psychiatry (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Discovery Research Portal (University of Dundee) (publishedVersion)
HAL (submittedVersion, other-oa)
Social Science Open Access Repository (GESIS – Leibniz Institute for the Social Sciences) (submittedVersion)
Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc)
Radboud Repository (Radboud University) (submittedVersion)
Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders: Eli Lilly and Company
Pfizer
Deutsche Forschungsgemeinschaft
Cilag
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: attention deficit hyperactivity disorder, ADHD genetics, candidate genes, dopamine signaling, noradrenergic system, serotonergic system, neurotransmitter transporters, SNAP-25, brain-derived neurotrophic factor, nerve growth factor, glial cell line-derived neurotrophic factor, genome-wide association study, neuronal migration, cell adhesion, cell division, heritability
MeSH terms: Adolescent, Cell Division, Child, Genetic Markers, Humans, Phenotype, Neurotransmitter Agents, Genetic Predisposition to Disease, Malformations of Cortical Development, Group II, Genome-Wide Association Study

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Molecular genetics of attention-deficit/hyperactivity disorder: an overview

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