Cited by 1,001Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorGenetic Associations and Epidemiology

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Molecular Genetics of Attention Deficit Hyperactivity Disorder

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Faraone, Stephen V., Mick, Eric·2010·Psychiatric Clinics of North America

DOI 10.1016/j.psc.2009.12.004PMC PMC2847260

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Abstract

Although twin studies demonstrate that ADHD is a highly heritable condition, molecular genetic studies suggest that the genetic architecture of ADHD is complex. The handful of genome-wide linkage and association scans that have been conducted thus far show divergent findings and are, therefore, not conclusive. Similarly, many of the candidate genes reviewed here (ie, DBH, MAOA, SLC6A2, TPH-2, SLC6A4, CHRNA4, GRIN2A) are theoretically compelling from neurobiological systems perspective but available data are sparse and inconsistent. However, candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder, with meta-analyses supportive of a role of the genes coding for DRD4, DRD5, SLC6A3, SNAP-25, and HTR1B in the etiology of ADHD.

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Background
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BackgroundInfluential
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Background
Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA)
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Tryptophan Hydroxylase 2 (TPH2) gene variants associated with ADHD
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The neurobiology of attention deficit/hyperactivity disorder
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Epinephrine and Norepinephrine Act as Potent Agonists at the Recombinant Human Dopamine D4 Receptor
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Confirmation That a Specific Haplotype of the Dopamine Transporter Gene Is Associated With Combined-Type ADHD
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Self-citation
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)
Manor, I., Tyano, S., Eisenberg, J., Bachner-Melman, R., Kotler, M., & Ebstein, R. P. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001078 · Cited by 128
Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD
Kent, L., Green, E., Hawi, Z., Kirley, A., Dudbridge, F., Lowe, N., Raybould, R., Langley, K., Bray, N. J., Fitzgerald, M., et al. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001696 · Cited by 127
Genome-wide association scan of the time to onset of Attention Deficit Hyperactivity Disorder
Lasky-Su, J., Anney, R., Neale, B., Franke, B., Zhou, K., Maller, J., Vásquez, A., Chen, W., Asherson, P., Buitelaar, J., et al. (2008) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30869 · Cited by 125 · cited 1×
“No finding achieved genomewide significance (ie, a P-value of <5x10 (8)) in the primary analysis of the ADHD diagnosis(160) but this analysis and several exploratory analyses implicated some novel genes that require further study.(161,162) Of interest, one of the exploratory analyses”
ResultSelf-citation
Genetics of hyperactivity.
Cantwell, D. P. (1975) · Journal of Child Psychology and Psychiatry and Allied Disciplines · doi:10.1111/j.1469-7610.1975.tb01275.x · Cited by 125
Examining for association between candidate gene polymorphisms in the dopamine pathway and attention‐deficit hyperactivity disorder: A family‐based study
Payton, A., Holmes, J., Barrett, J. H., Hever, T., Fitzpatrick, H., Trumper, A., Harrington, R., McGuffin, P., O’Donovan, M. C., Owen, M. J., et al. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1407 · Cited by 124 · cited 1×
“The 4 and 5 repeat alleles of this promoter-region VNTR were also significantly associated with ADHD in a sample of 133 Israeli families,(73) but not in a similarly-sized family-based study by Lawson and colleagues(74) A CA-repeat microsatellite in intron 2 was associated with ADHD(75) in 82 Chinese, but this was not…”
Background
Biased paternal transmission of SNAP-25 risk alleles in attention-deficit hyperactivity disorder
Kustanovich, V., Merriman, B., McGough, J., McCracken, J. T., Smalley, S. L., & Nelson, S. F. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001247 · Cited by 122
Linkage disequilibrium mapping at DAT1, DRD5 and DBH narrows the search for ADHD susceptibility alleles at these loci
Hawi, Z., Lowe, N., Kirley, A., Gruenhage, F., Nöthen, M. M., Greenwood, T. A., Kelsoe, J. R., Fitzgerald, M., & Gill, M. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001290 · Cited by 120 · cited 1×
“5 kb 50 to the transcription start site.(50) Meta-analysis of 14”
Background
Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD)
Quist, J. F., Barr, C. L., Schachar, R. J., Roberts, W., MALONE, M. A., Tannock, R., Basile, V. S., Beitchman, J. H., & Kennedy, J. L. (2000) · Molecular Psychiatry · doi:10.1038/sj.mp.4000779 · Cited by 118
Further evidence for the association between attention‐deficit/hyperactivity disorder and the dopamine‐β‐hydroxylase gene
Roman, T., Schmitz, M. D., Polanczyk, G. V., Eizirik, M., Rohde, L. A., & Hutz, M. H. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10194 · Cited by 115
Mutational analysis of the nicotinic acetylcholine receptor alpha 4 subunit gene in attention deficit/hyperactivity disorder: evidence for association of an intronic polymorphism with attention problems
Todd, R. D., Lobos, E. A., Sun, L.-W., & Neuman, R. J. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001257 · Cited by 115
Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5
Kustanovich, V., Ishii, J., Crawford, L., YANG, M. H., McGough, J. J., McCracken, J. T., Smalley, S. L., & Nelson, S. F. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001466 · Cited by 114
Additive effect of three noradrenergic genes (ADRA2A, ADRA2C, DBH) on attention‐deficit hyperactivity disorder and learning disabilities in Tourette syndrome subjects
Comings, D., Gade-Andavolu, R., Gonzalez, N., Blake, H., Wu, S., & MacMurray, J. P. (1999) · Clinical Genetics · doi:10.1034/j.1399-0004.1999.550304.x · Cited by 113
Association of the dopamine beta hydroxylase gene with attention deficit hyperactivity disorder: Genetic analysis of the Milwaukee longitudinal study
Smith, K. M., Daly, M. J., Fischer, M., Yiannoutsos, C. T., Bauer, L., Barkley, R. A., & NAVIA, B. A. (2003) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.20005 · Cited by 112
Genetic heterogeneity in catatonic schizophrenia: A family study
Beckmann, H., Franzek, E., & Stöber, G. (1996) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19960531)67:3 · Cited by 110
Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder
Lawson, D. C., Turic, D., Langley, K., Pay, H. M., Govan, C. F., Norton, N., Hamshere, M. L., Owen, M. J., O'Donovan, M. C., & Thapar, A. (2003) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.10002 · Cited by 108
Significance of Serotonin Transporter Gene 5-HTTLPR and Variable Number of Tandem Repeat Polymorphism in Attention Deficit Hyperactivity Disorder
Zoroglu, S., Erdal, M., Alaşehirli, B., Erdal, N., Si̇vasli, E., Tutkun, H., Savaş, H., & Herken, H. (2002) · Neuropsychobiology · doi:10.1159/000063667 · Cited by 108
Association Between the 5HT1B Receptor Gene (HTR1B) and the Inattentive Subtype of ADHD
Smoller, J. W., Biederman, J., Arbeitman, L., Doyle, A. E., Fagerness, J., Perlis, R. H., Sklar, P. B., & Faraone, S. V. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.07.017 · Cited by 105
Self-citation
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
Mill, J. S., Xu, X., Ronald, A., Curran, S. R., Price, T., Knight, J., Craig, I., Sham, P. C., Plomin, R. J., & Asherson, P. J. (2004) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30107 · Cited by 105 · cited 1×
“nately the direction of effect was in the opposite direction: the risk allele was associated with lower hyperactivity scores.(43)”
Result
Haplotype analysis of SNAP-25 suggests a role in the aetiology of ADHD
Mill, J. S., Richards, S., Knight, J., Curran, S. R., Taylor, E. A., & Asherson, P. J. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001482 · Cited by 104
Meta-analysis of family-based association studies between the dopamine transporter gene and attention deficit hyperactivity disorder
Purper-Ouakil, D., Wohl, M., Mouren, M., Verpillat, P., Adés, J., & Gorwood, P. (2005) · Psychiatric Genetics · doi:10.1097/00041444-200503000-00009 · Cited by 101
DRD4 gene variants and sustained attention in attention deficit hyperactivity disorder (ADHD): Effects of associated alleles at the VNTR and −521 SNP
Bellgrove, M. A., Hawi, Z., Lowe, N., Kirley, A., Robertson, I. H., & Gill, M. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30193 · Cited by 100 · cited 1×
“Thus, they conclude that such risk alleles have dissociable effects on cognition in ADHD children.(46)”
Background
Dopamine D3 receptor gene polymorphism and violent behavior: Relation to impulsiveness and ADHD-related psychopathology
Retz, W., R�sler, M., Supprian, T., Retz-Junginger, P., & Thome, J. (2003) · Journal of Neural Transmission · doi:10.1007/s00702-002-0805-5 · Cited by 100
Childhood Inattention and Dysphoria and Adult Obesity Associated with the Dopamine D4 receptor Gene in Overeating Women with Seasonal Affective Disorder
Levitan, R., Masellis, M., Lam, R. W., Muglia, P., Basile, V., Jain, U., Kaplan, A. S., Tharmalingam, S., Kennedy, S. H., & Kennedy, J. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300314 · Cited by 100
Is the α‐2A adrenergic receptor gene (ADRA2A) associated with attention‐deficit/hyperactivity disorder?
Roman, T., Schmitz, M. D., Polanczyk, G. V., Eizirik, M., Rohde, L. A., & Hutz, M. H. (2003) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.20018 · Cited by 100
Inferring candidate genes for Attention Deficit Hyperactivity Disorder (ADHD) assessed by the World Health Organization Adult ADHD Self-Report Scale (ASRS)
Reuter, M., Kirsch, P., & Hennig, J. (2005) · Journal of Neural Transmission · doi:10.1007/s00702-005-0366-5 · Cited by 99
Temperament and character profiles and the dopamine D4 receptor gene in ADHD.
Lynn, D., Lubke, G., Yang, M. H., McCracken, J., McGough, J., Ishii, J., Loo, S., Nelson, S., & Smalley, S. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.5.906 · Cited by 97 · cited 1×
“Two studies have provided evidence documenting strength of a DRD4-ADHD relationship relative to other phenotypes hypothesized to also be associated with DRD4: autism(48) and a novelty seeking temperament.(49) Grady and colleagues(48) found no”
Background
Association and linkage of α-2A adrenergic receptor gene polymorphisms with childhood ADHD
Park, L., Nigg, J. T., Waldman, I. D., Nummy, K. A., Huang‐Pollock, C. L., Rappley, M. D., & Friderici, K. H. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001605 · Cited by 95
Association study of a SNAP-25 microsatellite and attention deficit hyperactivity disorder.
Mill, J., Curran, S., Kent, L., Gould, A., Huckett, L., Richards, S., Taylor, E., & Asherson, P. (2002) · American journal of medical genetics · doi:10.1002/ajmg.10253 · Cited by 94
Follow-up of genetic linkage findings on chromosome 16p13: evidence of association of N-methyl-D aspartate glutamate receptor 2A gene polymorphism with ADHD
Turic, D., Langley, K., Mills, S., Stephens, M., Lawson, D. C., Govan, C., Williams, N. M., van den Bree, M. V. D., Craddock, N., Kent, L., et al. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001387 · Cited by 91
Association analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample: Preferential transmission of the MAO‐A 941G allele to affected children
Domschke, K., Sheehan, K., Lowe, N., Kirley, A., Mullins, C., O’Sullivan, R. J., Freitag, C., Becker, T., Conroy, J., Fitzgerald, M., et al. (2005) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30158 · Cited by 89 · cited 1×
“The 4 and 5 repeat alleles of this promoter-region VNTR were also significantly associated with ADHD in a sample of 133 Israeli families,(73) but not in a similarly-sized family-based study by Lawson and colleagues(74) A CA-repeat microsatellite in intron 2 was associated with ADHD(75) in 82 Chinese, but this was not…”
Background
The serotonin transporter gene as a QTL for ADHD
Curran, S. R., Purcell, S., Craig, I., Asherson, P. J., & Sham, P. C. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30118 · Cited by 87
Association of dopamine D4 receptor (DRD4) gene with attention-deficit/hyperactivity disorder (ADHD) in a high-risk community sample: a longitudinal study from birth to 11 years of age
El-Faddagh, M., Laucht, M., Maras, A., Vöhringer, L., & Schmidt, M. H. (2004) · Journal of neural transmission · doi:10.1007/s00702-003-0054-2 · Cited by 87
Collaborative analysis of DRD4 and DAT genotypes in population-defined ADHD subtypes.
Todd, R., Huang, H.-Y., Smalley, S., Nelson, S., Willcutt, E., Pennington, B., Smith, S. D., Faraone, S., & Neuman, R. J. (2005) · Journal of Child Psychology and Psychiatry and Allied Disciplines · doi:10.1111/j.1469-7610.2005.01517.x · Cited by 86
Self-citation
Lack of association of dopamine D4 receptor gene polymorphisms with ADHD subtypes in a population sample of twins.
Todd, R. D., Neuman, R. J., Lobos, E., Jong, Y. I., Reich, W., & Heath, A. C. (2001) · American journal of medical genetics · doi:10.1002/ajmg.1403 · Cited by 86
Meta-analysis of Association Between a Catechol-O-Methyltransferase Gene Polymorphism and Attention Deficit Hyperactivity Disorder
Cheuk, D., & Wong, V. (2006) · Behavior Genetics · doi:10.1007/s10519-006-9076-5 · Cited by 85 · cited 1×
“a weak association with ADHD and the dopamine transporter gene (SLC6A3, 480bp VNTR in the 30 untranslated region [UTR]),(18,21,22) but no association with the catechol-O-methyltransferase gene (COMT, Val108Met polymorphism).(23)”
Background
Two dopamine genes related to reports of childhood retrospective inattention and conduct disorder symptoms
Rowe, D., Stever, C., Chase, D. S., Sherman, S. L., Abramowitz, A. J., & Waldman, I. D. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000874 · Cited by 81
A comparison of molecular alterations in environmental and genetic rat models of ADHD: A pilot study
DasBanerjee, T., Middleton, F. A., Berger, D. F., Lombardo, J. P., Sagvolden, T., & Faraone, S. V. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30877 · Cited by 81 · cited 1×
“The lack of significant results from the IMAGE project(91) is consistent with the negative meta-analysis conducted by Cheuk and colleagues(23) Although these association studies rule out a simple role for the Val108Met polymorphism in the etiology of ADHD, it is of note that COMT hass been found to be highly up-regula…”
ResultSelf-citation
The norepinephrine transporter gene and attention‐deficit hyperactivity disorder
Barr, C. L., Kroft, J., Feng, Y., Wigg, K. G., Roberts, W., MALONE, M. A., Ickowicz, A., Schachar, R. J., Tannock, R., & Kennedy, J. L. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10193 · Cited by 80
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
Self-citation
Nature, Nurture, and Attention Deficit Hyperactivity Disorder
Faraone, S. V., & Biederman, J. (2000) · Developmental Review · doi:10.1006/drev.2000.0515 · Cited by 76 · cited 1×
“had ADHD to be increased by between two- and eightfold, with similarly elevated risk among siblings.(3) Faraone and colleagues(4) extended these findings to families ascertained through adult probands meeting Diagnostic and Statistical Manual of Mental”
BackgroundSelf-citation
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
Self-citation
Genotypic interaction between DRD4 and DAT1 loci is a high risk factor for attention‐deficit/hyperactivity disorder in Chilean families
Carrasco, X., Rothhammer, P., Moraga, M., Henríquez, H., Chakraborty, R., Aboitiz, F., & Rothhammer, F. (2006) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30259 · Cited by 74
The DRD2 TaqI polymorphism and symptoms of attention deficit hyperactivity disorder
Rowe, D. C., Oord, E. V. D., Stever, C., Giedinghagen, L. N., Gard, J. M. C., Cleveland, H., Gilson, M., Terris, S. T., Mohr, J., Sherman, S., et al. (1999) · Molecular Psychiatry · doi:10.1038/sj.mp.4000567 · Cited by 71
Linkage Analysis of Attention Deficit Hyperactivity Disorder
Faraone, S., Doyle, A., Lasky-Su, J., Sklar, P., D'Angelo, E., Gonzalez-Heydrich, J., Kratochvil, C., Mick, E., Klein, K. L., Rezac, A. J., et al. (2008) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30631 · Cited by 69
Self-citation
The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder
Feng, Y., Crosbie, J., Wigg, K., Pathare, T., Ickowicz, A., Schachar, R., Tannock, R., Roberts, W., Malone, M., Swanson, J., et al. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001762 · Cited by 68
Association of the low-activity COMT 158Met allele with ADHD and OCD in subjects with velocardiofacial syndrome
(2007) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145706006699 · Cited by 67
Pedigree disequilibrium test (PDT) replicates association and linkage between DRD4 and ADHD in multigenerational and extended pedigrees from a genetic isolate
Arcos‐Burgos, M., Castellanos, F. X., Konecki, D. S., Lopera, F. J., Pineda, D. A., Palacio, J. D., Rapoport, J. L., Berg, K., Wilson, J., & Muenke, M. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001396 · Cited by 67 · cited 1×
“isolated community in Columbia implicated 8q12, 11q23, 4q13, 17p11, 12q23, and 8p23.(12) Pooled analyses(10,11) suggest that the genetic background in the differing populations is distinct and that the lack of consistent findings is a reflection of this between-population heterogeneity,(13) but did identify an area of…”
Investigation of variation in SNAP‐25 and ADHD and relationship to co‐morbid major depressive disorder
Kim, J.-W., Biederman, J., Arbeitman, L., Fagerness, J., Doyle, A., Petty, C., Perlis, R., Purcell, S., Smoller, J. W., Faraone, S., et al. (2007) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30522 · Cited by 65 · cited 3×
“Stratification by psychiatric comorbidity further suggested that subjects with ADHD and comorbid depression may demonstrate stronger association with SNPs in SNAP-25.”
BackgroundInfluentialSelf-citation
Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a positional candidate for attention-deficit/hyperactivity disorder in the 16p13 region
Adams, J. H., Crosbie, J., Wigg, K., Ickowicz, A., Pathare, T., Roberts, W., Malone, M., Schachar, R., Tannock, R., Kennedy, J., et al. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001455 · Cited by 65
Characterizing the ADHD phenotype for genetic studies
Stevenson, J., Asherson, P. J., Hay, D. A., Lévy, F., Swanson, J., Thapar, A., & Willcutt, E. (2005) · Developmental Science · doi:10.1111/j.1467-7687.2005.00398.x · Cited by 63
DAT1, DRD4, and DRD5 polymorphisms are not associated with ADHD in Dutch families
Bakker, S., van der Meulen, E. M., Oteman, N., Schelleman, H., Pearson, P. L., Buitelaar, J., & Sinke, R. (2005) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30089 · Cited by 63
Family‐based association study between brain‐derived neurotrophic factor gene polymorphisms and attention deficit hyperactivity disorder in UK and Taiwanese samples
Xu, X., Mill, J. S., Zhou, K., Brookes, K. J., Chen, C., & Asherson, P. J. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30406 · Cited by 61 · cited 1×
“found significant over transmission of the C720T allele in Taiwanese, but not UK, ADHD families.(159) Twenty SNPs in the BDNF gene were tagged for the IMAGE project, but none were statistically significantly associated with ADHD.”
Background
A Longitudinal Look at Parent–Child Diagnostic Agreement in Youth Treated for Anxiety Disorders
Safford, S. M., Kendall, P. C., Flannery-Schroeder, E. C., Webb, A., & Sommer, H. (2005) · Journal of Clinical Child & Adolescent Psychology · doi:10.1207/s15374424jccp3404_16 · Cited by 59
Linkage studies between attention‐deficit hyperactivity disorder and the monoamine oxidase genes
Jiang, S., Xin, R., Lin, S., Qian, Y., Tang, G., Wang, D., & Wu, X. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.10098 · Cited by 57
Polymorphism of the serotonin-2A receptor gene (HTR2A) associated with childhood attention deficit hyperactivity disorder (ADHD) in adult women with seasonal affective disorder.
Levitan, R., Masellis, M., Basile, V., Lam, R. W., Jain, U., Kaplan, A. S., Kennedy, S. H., Siegel, G., Walker, M., Vaccarino, F., et al. (2002) · Journal of Affective Disorders · doi:10.1016/s0165-0327(01)00372-x · Cited by 57
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
Li, J., Wang, Y., Zhou, R., Zhang, H., Yang, L., Wang, B., & Faraone, S. V. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30373 · Cited by 57
Self-citation
The adrenergic receptor -A gene (ADRA2A) and neuropsychological executive functions as putative endophenotypes for childhood ADHD
Waldman, I. D., Nigg, J. T., Gizer, I. R., Park, L. C., Rappley, M. D., & Friderici, K. H. (2006) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/cabn.6.1.18 · Cited by 56
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
Family-based association study of serotonergic candidate genes and attention-deficit/hyperactivity disorder in a German sample
Heiser, P., Dempfle, A., Friedel, S., Konrad, K., Hinney, A., Kiefl, H., Walitza, S., Bettecken, T., Saar, K., Linder, M., et al. (2006) · Journal of Neural Transmission · doi:10.1007/s00702-006-0584-5 · Cited by 55 · cited 1×
“A coding polymorphism in the HTR2A receptor gene (His452Tyr) was associated with ADHD in,(118,122) but not in.(113,116) Li and colleagues(124) found significant over-transmission of the C-759T/G-697C haplotype within the HTR2C gene, but no association was observed in Bobb and colleagues(111) or in the IMAGE project.”
Background
Multiple marker analysis at the promoter region of the DRD4 gene and ADHD: Evidence of linkage and association with the SNP −616
Lowe, N., Kirley, A., Mullins, C., Fitzgerald, M., Gill, M., & Hawi, Z. (2004) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30071 · Cited by 54
Linkage study of the α2A adrenergic receptor in attention-deficit hyperactivity disorder families
Xu, C., Schachar, R. J., Tannock, R., Roberts, W., MALONE, M. A., Kennedy, J. L., & Barr, C. L. (2001) · American Journal of Medical Genetics · doi:10.1002/1096-8628(2001)9999:9999 · Cited by 53
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
Attention deficit hyperactivity disorder and the gene for dopamine Beta-hydroxylase.
Wigg, K., Zai, G., Schachar, R., Tannock, R., Roberts, W., Malone, M., Kennedy, J., & Barr, C. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.6.1046 · Cited by 52
Further evidence of the involvement of alpha-2A-adrenergic receptor gene (ADRA2A) in inattentive dimensional scores of attention-deficit/hyperactivity disorder
Román, T., Polanczyk, G. V., Zeni, C., Genro, J., Rohde, L., & Hutz, M. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001743 · 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
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
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
Self-citation
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
Self-citation
Serotonin genes and attention deficit/hyperactivity disorder in a Brazilian sample: Preferential transmission of the HTR2A 452His allele to affected boys
Guimarães, A. P. M., Zeni, C., Polanczyk, G. V., Genro, J. P., Roman, T., Rohde, L. A., & Hutz, M. H. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30400 · Cited by 44
Possible involvement of alpha‐2A adrenergic receptors in attention deficit hyperactivity disorder: Radioligand binding and polymorphism studies
Deupree, J., Smith, S. D., Kratochvil, C. J., Bohac, D., Ellis, C., Polaha, J. A., & Bylund, D. B. (2006) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30371 · Cited by 43
Family-based association study of DAT1 and DRD4 polymorphism in Korean children with ADHD.
Kim, Y. S., Leventhal, B., Kim, S.-J., Kim, B.-N., Cheon, K., Yoo, H., Kim, S.-J., Badner, J., & Cook, E. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.08.025 · Cited by 43 · cited 1×
“67).(30) Carrasco and colleagues(31) also failed to document an”
Background
Clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder
KIM, J.-W., PARK, C.-S., HWANG, J.-W., SHIN, M.-S., HONG, K.-E., CHO, S.-C., & KIM, B.-N. (2006) · Alcohol and Alcoholism · doi:10.1093/alcalc/agl034 · Cited by 43
Association of dopamine D4 receptor (DRD4) polymorphisms with attention deficit hyperactivity disorder in Indian population
Bhaduri, N., Das, M., Sinha, S., Chattopadhyay, A., Gangopadhyay, P. K., Chaudhuri, K., Singh, M., & Mukhopadhyay, K. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30225 · Cited by 43
Sequence variants of theDRD4 gene in autism: Further evidence that rareDRD4 7R haplotypes are ADHD specific
Grady, D. L., Harxhi, A., Smith, M., Flodman, P. L., Spence, M. A., Swanson, J. M., & Moyzis, R. K. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30182 · Cited by 43
Association of attention-deficit/hyperactivity disorder with serotonin 4 receptor gene polymorphisms in Han Chinese subjects
Li, J., Wang, Y., Zhou, R., Wang, B., Zhang, H., Yang, L., & Faraone, S. V. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.02.053 · Cited by 43
Self-citation
A transmission disequilibrium test of the Ser9/Gly dopamine D3 receptor gene polymorphism in adult attention-deficit hyperactivity disorder
Muglia, P., Jain, U., & Kennedy, J. L. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00438-7 · Cited by 41 · cited 1×
“Ser9Gly polymorphism were also reported in a UK family-based study of 105 families(69) and a study of 39 families of ADHD adults.(85) Comings and colleagues(86) also found no evidence for association with ADHD and comorbid Tourrette Syndrome.”
Background
Attention-deficit hyperactivity disorder and the adrenergic receptors α1C and α2C
Barr, C., Wigg, K., Zai, G., Roberts, W., Malone, M., Schachar, R., Tannock, R., & Kennedy, J. L. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000863 · Cited by 41
No evidence for the association of DRD4 with ADHD in a Taiwanese population within-family study
Brookes, K., Xu, X.-H., Chen, C.-K., Huang, Y.-S., Wu, Y., & Asherson, P. (2005) · BMC Medical Genetics · doi:10.1186/1471-2350-6-31 · Cited by 40
A “line item” approach to the identification of genes involved in polygenic behavioral disorders: The Adrenergic α2A (ADRA2A) gene
Comings, D., Gonzalez, N., Cheng, L.-P., & Macmurray, J. (2003) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.10056 · Cited by 39
Lack of association between the tryptophan hydroxylase gene A218C polymorphism and attention‐deficit hyperactivity disorder in Chinese Han population
Tang, G., Ren, D., Xin, R., Qian, Y., Wang, D., & Jiang, S. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1471 · Cited by 39 · cited 1×
“One study of 69 Han Chinese trios found no association with a SNP (A218C) in intron 7.(137) A second study examined two SNPs among more than 350 Han Chinese youth with ADHD, with and without learning disability, and their families.”
Background
Non-stimulant treatments for ADHD
Biederman, J., & Spencer, T. (2009) · European Child and Adolescent Psychiatry · doi:10.1007/s007870070019 · Cited by 38
Dopa decarboxylase gene polymorphisms and attention deficit hyperactivity disorder (ADHD): no evidence for association in the Irish population
Hawi, Z., Foley, D. L., Kirley, A., McCarron, M., Fitzgerald, M., & Gill, M. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000903 · Cited by 36
Association between polymorphisms in serotonin 2C receptor gene and attention-deficit/hyperactivity disorder in Han Chinese subjects.
Li, J., Wang, Y.-F., Zhou, R., Zhang, H.-B., Yang, L., Wang, B., & Faraone, S. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.08.022 · Cited by 36
Self-citation
Contribution of 5‐HT2A receptor gene ‐1438A>G polymorphism to outcome of attention‐deficit/hyperactivity disorder in adolescents
Li, J., Kang, C., Wang, Y., Zhou, R., Wang, B., Guan, L., Yang, L., & Faraone, S. V. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30320 · Cited by 36
Self-citation
Family‐based association study of serotonin transporter gene polymorphisms in attention deficit hyperactivity disorder: No evidence for association in UK and Taiwanese samples
Xu, X., Mill, J. S., Chen, C., Brookes, K. J., Taylor, E. A., & Asherson, P. J. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30203 · Cited by 34
Family‐based association study of the serotonin transporter gene polymorphisms in Korean ADHD trios
Kim, S., Badner, J. A., Cheon, K.-A. A., Kim, B., Yoo, H., Kim, S. J., Cook, E. H., LEVENTHAL, B. L., & Kim, Y. S. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30214 · Cited by 32
Linkage disequilibrium analysis of the dopamine beta-hydroxylase gene in persistent attention deficit hyperactivity disorder
Inkster, B., Muglia, P., Jain, U., & Kennedy, J. (2004) · Psychiatric Genetics · doi:10.1097/01.ypg.0000107932.32051.1c · Cited by 31
Association study of the nicotinic acetylcholine receptor α4 subunit gene, CHRNA4, in attention‐deficit hyperactivity disorder
Lee, J., Laurin, N., Crosbie, J., Ickowicz, A., Pathare, T., MALONE, M. A., Kennedy, J. L., Tannock, R., Schachar, R. J., & Barr, C. L. (2007) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2007.00325.x · Cited by 31
Association between tryptophan hydroxylase gene polymorphisms and attention deficit hyperactivity disorder in Chinese Han population
Li, J., Wang, Y., Zhou, R., Zhang, H., Yang, L., Wang, B., & Faraone, S. V. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30260 · Cited by 31 · cited 1×
“A second study examined two SNPs among more than 350 Han Chinese youth with ADHD, with and without learning disability, and their families.(138,139) Although neither SNP showed biased transmission individually, a haplotype composed of the A218 and G-6526 alleles appeared to be under-trans-”
BackgroundSelf-citation
Evaluation of linkage of markers on chromosome 6p with schizophrenia in Taiwanese families
Hwu, H., Lin, M., Lee, P.-C., Lee, S. F. ‐., Ouyang, W., & Liu, C. (2000) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(20000207)96:1 · Cited by 30
Association study between the monoamine oxidase A gene and attention deficit hyperactivity disorder in Taiwanese samples
Xu, X.-H., Brookes, K., Chen, C.-K., Huang, Y.-S., Wu, Y., & Asherson, P. (2007) · BMC Psychiatry · doi:10.1186/1471-244x-7-10 · Cited by 30
DNA pooling analysis of ADHD and genes regulating vesicle release of neurotransmitters
Brookes, K. J., Knight, J., Xu, X., & Asherson, P. J. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30216 · Cited by 30
No association between TPH2 gene polymorphisms and ADHD in a UK sample
Sheehan, K., Hawi, Z., Gill, M., & Kent, L. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.10.043 · Cited by 29 · cited 1×
“Brookes and colleagues also reported an association with rs1007023 which was in perfect LD with rs1386497 from Sheehan and colleagues(39) However, Brookes and colleagues did not replicate the finding reported by Walitza and colleagues(141) and Sheehan and colleagues was not able to replicate their earlier findings in…”
Result
Adrenergic alpha 2C receptor genomic organization: Association study in adult ADHD
Luca, V. D., Muglia, P., Vincent, J., Lanktree, M., Jain, U., & Kennedy, J. (2004) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.20171 · Cited by 25 · cited 2×
“Two subsequent family-based analyses showed no evidence of association.(105,106) The former study also exam-”
Background
No association of attention-deficit/hyperactivity disorder with genes of the serotonergic pathway in Han Chinese subjects
Li, J., Wang, Y., Zhou, R., Wang, B., Zhang, H., Yang, L., & Faraone, S. V. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.04.036 · Cited by 20
Self-citation
Lack of significant association between −1021C→T polymorphism in the dopamine beta hydroxylase gene and attention deficit hyperactivity disorder
Bhaduri, N., & Mukhopadhyay, K. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.03.036 · Cited by 19 · cited 1×
“A -1021C>T polymorphism in the 50 flanking region of DBH has been shown to account for as much as 50% of plasma DBH activity and was associated with ADHD in the Han Chinese,(71) but not in a sample of Indian ADHD children.(67) Finally,”
Background
The serotonin 5‐HT1D receptor gene and attention‐deficit hyperactivity disorder in Chinese Han subjects
Li, J., Zhang, X., Wang, Y., Zhou, R., Zhang, H., Yang, L., Wang, B., & Faraone, S. V. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30364 · Cited by 18 · cited 2×
“significant under transmission of the C83097T/G83198A haplotype in the HTR4 gene, but no association with markers in HTR5A and HTR6(120) or HTR1D.(126) Genes for additional serotonin receptors (HTR1E and HTR3B) evaluated in the IMAGE project(39) have also failed to yield any significant association with ADHD.”
BackgroundSelf-citation
The broad autism phenotype: A complementary strategy for molecular genetic studies of autism
(2001) · doi:10.1002/1096-8628(20010108)105:1

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Research works printed but not linked: 10

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See all 1,001

Authors: Faraone, S. V., & Mick, E.
Affiliations: SUNY Upstate Medical University (US)
Harvard University (US)
Corresponding author: Faraone, Stephen V.
ORCID: Faraone, Stephen V.
Mick, Eric
Venue: Psychiatric Clinics of North America
Publisher: Elsevier BV
Published: 2010-03
Volume: 33
Issue: 1
Pages: 159-180
ISSN: 0193-953X (ISSN-L)
DOI: 10.1016/j.psc.2009.12.004
PMC: PMC2847260
OpenAlex: W2168200222
Cited by: 411
References: 170
Citations by year: 2026: 5 · 2025: 11 · 2024: 12 · 2023: 26 · 2022: 16 · 2021: 20 · 2020: 15 · 2019: 17 · 2018: 24 · 2017: 30 · 2016: 33 · 2015: 32 · 2014: 45 · 2013: 40 · 2012: 39
FWCI: 5.44
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Psychiatric Clinics of North America (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (R01MH066877, R13MH059126)
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, genetic etiology, heritability, genome-wide linkage analysis, genome-wide association study, candidate genes, DBH, monoamine oxidase A, norepinephrine transporter, serotonin transporter, CHRNA4, GRIN2A, DRD4, DRD5, dopamine transporter, SNAP-25, 5-HT1B receptor, dopamine, monoamine transporters, neurotransmitter systems
MeSH terms: Attention Deficit Disorder with Hyperactivity, Humans, Molecular Biology, Twins, Gene Expression, Prevalence, Genome-Wide Association Study

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Molecular Genetics of Attention Deficit Hyperactivity Disorder

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