Effect of candidate gene polymorphisms on the course of attention deficit hyperactivity disorder
Open accessAbstract
The main aim of this study was to examine the association between attention-deficit hyperactivity disorder (ADHD)-associated genes and the course of ADHD. Subjects were derived from identically designed case-control family studies of boys and girls with ADHD and a genetic linkage study of families with children with ADHD. Caucasian probands and family members with ADHD and with available genetic data were included in this analysis (N=563). The course of ADHD was compared in subjects with and without putative risk alleles (DRD4 7-repeat allele, DAT1 10-repeat allele, and 5HTTLPR long allele). The persistence of ADHD (full or subthreshold diagnosis in the last month) was plotted using Kaplan-Meier survival functions and tested with Cox proportional hazard models. Survival analyses revealed that by 25 years of age 76% of subjects with a DRD4 7-repeat allele were estimated to have significantly more persistent ADHD compared with 66% of subjects without the risk allele. In contrast, there were no significant associations between the course of ADHD and the DAT1 10-repeat allele (P=0.94) and 5HTTLPR long allele. Our findings suggest that the DRD4 7-repeat allele is associated with a more persistent course of ADHD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Evidence on the association of the DRD4 7-repeat allele with persistent ADHD is inconsistent, with some studies finding an association and others finding that patients with persistent ADHD symptoms were less likely to have the allele.
“Some studies have found that the DRD4 7-repeat (7R) allele was associated with persistent ADHD (Biederman et al., 2009; Langley et al., 2009), while other studies found that the patients with persistent ADHD symptoms were less likely have DRD4 7R allele (Shaw et al., 2007).”
From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Biederman et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
(1967) · Project Euclid (Cornell University) · Cited by 4,720 · see citing works
Structured clinical interview for DSM-IV axis I disorders : SCID-I : clinical version : scoresheet
First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (1997) · American Psychiatric Press eBooks · Cited by 3,101 · see citing works
Proceedings of the Fifth Berkeley Symposium on Mathematical Statistics and Probability; Vol. IV
Roy, H. L. L., LeCam, L. M., & Neyman, J. (1969) · Revue de l Institut International de Statistique / Review of the International Statistical Institute · doi:10.2307/1402306 · Cited by 2,878 · see citing works
Molecular genetics of attention-deficit/hyperactivity disorder
Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A., & Sklar, P. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.11.024 · Cited by 2,357 · see citing works
Self-citationFARAONE, S. V., BIEDERMAN, J., & MICK, E. (2006) · Psychological Medicine · doi:10.1017/s003329170500471x · Cited by 2,267 · see citing works
Self-citationBiederman, J. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.5.816 · Cited by 1,498 · see citing works
Self-citationYoung Adult Outcome of Hyperactive Children: Adaptive Functioning in Major Life Activities
Barkley, R. A., Fischer, M., Smallish, L., & Fletcher, K. (2006) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000189134.97436.e2 · Cited by 1,027 · see citing works
BIEDERMAN, J., MONUTEAUX, M. C., MICK, E., SPENCER, T., WILENS, T. E., SILVA, J. M., SNYDER, L. E., & FARAONE, S. V. (2006) · Psychological Medicine · doi:10.1017/s0033291705006410 · Cited by 850 · see citing works
Self-citationFaraone, S., Doyle, A., Mick, E., & Biederman, J. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.7.1052 · Cited by 740 · see citing works
Self-citationLi, D.-W., Sham, P., Owen, M., & He, L. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl152 · Cited by 611 · see citing works
Mice Lacking Dopamine D4 Receptors Are Supersensitive to Ethanol, Cocaine, and Methamphetamine
Rubinstein, M., Phillips, T. J., Bunzow, J. R., Falzone, T. L., Dziewczapolski, G., Zhang, G., Fang, Y., Larson, J. L., McDougall, J. A., Chester, J. A., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80365-7 · Cited by 473 · see citing works
Keck, P., McElroy, S. L., Strakowski, S. M., West, S. A., Sax, K. W., Hawkins, J. M., Bourne, M. L., & Haggard, P. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.5.646 · Cited by 456 · see citing works
Dopamine D4 Receptor-Knock-Out Mice Exhibit Reduced Exploration of Novel Stimuli
Dulawa, S. C., Grandy, D. K., Low, M. J., Paulus, M. P., & Geyer, M. A. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-21-09550.1999 · Cited by 432 · see citing works
Molecular Genetics of Attention Deficit Hyperactivity Disorder
Faraone, S. V., & Mick, E. (2010) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2009.12.004 · Cited by 411 · cited 4× · see citing works
“Multiple candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder (Faraone et al., 2005; Li et al., 2006; Purper-Ouakil et al., 2005; Yang et al., 2007).”
InfluentialSelf-citation(1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.3.431 · Cited by 289 · see citing works
Self-citationShaw, P., Gornick, M., Lerch, J., Addington, A., Seal, J., Greenstein, D., Sharp, W., Evans, A., Giedd, J. N., Castellanos, F. X., et al. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.8.921 · Cited by 242 · see citing works
Genetics of Attention Deficit Hyperactivity Disorder
Mick, E. O., & Faraone, S. V. (2008) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2007.11.011 · Cited by 230 · see citing works
Self-citationDopamine system genes and attention deficit hyperactivity disorder: a meta-analysis
Maher, B. S., Marazita, M. L., Ferrell, R. E., & Vanyukov, M. M. (2002) · Psychiatric Genetics · doi:10.1097/00041444-200212000-00003 · Cited by 224 · see citing works
Dopamine DRD4 receptor polymorphism and attention deficit hyperactivity disorder
Rowe, D., Stever, C., Giedinghagen, L. N., Gard, J. M. C., Cleveland, H. H., Terris, S. T., Mohr, J., Sherman, S. L., Abramowitz, A. J., & Waldman, I. D. (1998) · Molecular Psychiatry · doi:10.1038/sj.mp.4000432 · Cited by 213 · see citing works
Larsson, J., Larsson, H., & Lichtenstein, P. (2004) · Journal of the American Academy of Child and Adolescent Psychiatry · doi:10.1097/01.chi.0000135622.05219.bf · Cited by 201 · see citing works
Faraone, S. V., Biederman, J., & Monuteaux, M. C. (2000) · Genetic Epidemiology · doi:10.1002/(sici)1098-2272(200001)18:1 · Cited by 195 · see citing works
Self-citationMcCracken, J. T., Smalley, S. L., McGough, J. J., Crawford, L., Del'Homme, M., Cantor, R. M., Liu, A., & Nelson, S. F. (2000) · Molecular Psychiatry · doi:10.1038/sj.mp.4000770 · Cited by 189 · see citing works
Yang, B., Chan, R., Jing, J., Li, T., Sham, P., & Chen, R. Y. L. (2007) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30453 · Cited by 184 · see citing works
Biederman, J., Monuteaux, M. C., Mick, E. O., Spencer, T. J., Wilens, T. E., Klein, K. L., Price, J., & Faraone, S. V. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.031 · Cited by 168 · see citing works
Self-citationKuntsi, J., Rijsdijk, F., Ronald, A., Asherson, P., & Plomin, R. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.12.032 · Cited by 140 · see citing works
Barkley, R. A., Smith, K. M., Fischer, M., & NAVIA, B. A. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30326 · Cited by 114 · see citing works
Mill, J. S., Caspi, A., Williams, B. S., Craig, I., Taylor, A., Polo-Tomás, M., Berridge, C. W., Poulton, R., & Moffitt, T. E. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.4.462 · Cited by 102 · see citing works
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 · see citing works
Johansson, S., Halleland, H., Halmøy, A., Jacobsen, K. K., Landaas, E. T., Dramsdahl, M., Fasmer, O. B., Bergsholm, P., Lundervold, A. J., Gillberg, C., et al. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30662 · Cited by 91 · see citing works
Correspondence Between DSM-III-R and DSM-IV Attention-Deficit/Hyperactivity Disorder
Biederman, J., Faraone, S. V., Weber, W. J., Russell, R. L., Rater, M. A., & Park, K. S. (1997) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199712000-00016 · Cited by 82 · see citing works
Self-citationAssociation of the dopamine transporter (<i>SLC6A3/DAT1</i>) gene 9–6 haplotype with adult ADHD
Franke, B., Hoogman, M., Arias Vasquez, A., Heister, J. G. A. M., Savelkoul, P. J., Naber, M., Scheffer, H., Kiemeney, L. A., Kan, C. C., Kooij, J. J. S., et al. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30861 · Cited by 77 · cited 1× · see citing works
“Most recently, Franke et al. (2008) found that a 9-6DAT1 haplotypewas associatedwith adult ADHD, and Johansson et al. (2007) showed an association between adult ADHD and DRD5 but not DAT1 or DRD4.”
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 · see citing works
Self-citationPrice, T. S., Simonoff, E. A., Asherson, P. J., Curran, S. R., Kuntsi, J., Waldman, I. D., & Plomin, R. J. (2005) · Behavior Genetics · doi:10.1007/s10519-004-1013-x · Cited by 66 · see citing works
D4 receptor deficiency in mice has limited effects on impulsivity and novelty seeking
Helms, C. M., Gubner, N. R., Wilhelm, C., Mitchell, S. H., & Grandy, D. K. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.03.013 · Cited by 58 · see citing works
Alcohol abuse and attention deficit disorder.
Manshadi, M., Lippmann, S., O'Daniel, R., & Blackman, A. (1983) · PubMed · Cited by 58 · see citing works
Lasky-Su, J., Lange, C., Biederman, J., Tsuang, M., Doyle, A., Smoller, J. W., Laird, N., & Faraone, S. (2008) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30567 · Cited by 52 · see citing works
Self-citationLangley, 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 · see citing works
Lasky-Su, J., Banaschewski, T., Buitelaar, J., Franke, B., Brookes, K., Sonuga-Barke, E., Ebstein, R., Eisenberg, J., Gill, M., Manor, I., et al. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.03.006 · Cited by 29 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The genetics of attention deficit/hyperactivity disorder in adults, a review
on behalf of the International Multicentre persistent ADHD CollaboraTion (IMpACT), Franke, B., Faraone, S. V., Asherson, P., Buitelaar, J., Bau, C. H. D., Ramos-Quiroga, J. A., Mick, E., Grevet, E. H., Johansson, S., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.138 · Cited by 432 · see citing works
Self-citationA Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD)
Luo, Y., Weibman, D., Halperin, J. M., & Li, X. (2019) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2019.00042 · Cited by 394 · see citing works
“Some studies have found that the DRD4 7-repeat (7R) allele was associated with persistent ADHD (Biederman et al., 2009; Langley et al., 2009), while other studies found that the patients with persistent ADHD symptoms were less likely have DRD4 7R allele (Shaw et al.”
ResultCaye, A., Spadini, A. V., Karam, R. G., Grevet, E. H., Rovaris, D. L., Bau, C. H. D., Rohde, L. A., & Kieling, C. (2016) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-016-0831-8 · Cited by 210 · see citing works
Developmental Twin Study of Attention Problems: High Heritabilities Throughout Development
Chang, Z., Lichtenstein, P., Asherson, P. J., & Larsson, H. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.287 · Cited by 194 · see citing works
Does neurocognitive functioning predict future or persistence of ADHD? A systematic review
van Lieshout, M., Luman, M., Buitelaar, J., Rommelse, N. N. J., & Oosterlaan, J. (2013) · Clinical Psychology Review · doi:10.1016/j.cpr.2013.02.003 · Cited by 133 · see citing works
Psychopathological aspects of dopaminergic gene polymorphisms in adolescence and young adulthood
Nemoda, Z., Szekely, A., & Sasvari-Szekely, M. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.04.002 · Cited by 78 · see citing works
- Authors
- Biederman, J., Petty, C. R., Ten Haagen, K. S., Small, J., Doyle, A. E., Spencer, T., Mick, E., Monuteaux, M. C., Smoller, J. W., & Faraone, S. V.
- Affiliations
- Massachusetts General Hospital (US)
- SUNY Upstate Medical University (US)
- Corresponding author
- Biederman, Joseph
- Venue
- Psychiatry Research
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 170
- Issue
- 2-3
- Pages
- 199-203
- ISSN
- 0165-1781 (ISSN-L)
- PMC
- PMC3752702
- OpenAlex
- W2117716763
- Cited by
- 38
- References
- 38
- Citations by year
- 2025: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 6 · 2014: 7 · 2013: 6 · 2012: 3
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Psychiatry Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01HD036317, R01HD037694, R01HD037999, R01MH050657, R01MH066877)
- 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, candidate gene polymorphisms, risk alleles
- MeSH terms
- Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Family Health, Female, Gene Frequency, Genotype, Humans, Longitudinal Studies, Male, Polymorphism, Genetic, Linkage Disequilibrium, Survival Analysis, Case-Control Studies, Minisatellite Repeats, Genetic Predisposition to Disease, Dopamine Plasma Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins, Receptors, Dopamine D4, Kaplan-Meier Estimate, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
