Association of the dopamine receptor D4 (DRD4) gene 7‐repeat allele with children with attention‐deficit/hyperactivity disorder (ADHD): An update
Open accessAbstract
Polymorphisms of the dopamine receptor D4 gene DRD4, 11p15.5, have previously been associated with attention-deficit/hyperactivity disorder (ADHD) [Bobb et al., 2005; Am J Med Genet B Neuropsychiatr Genet 132:109-125; Faraone et al., 2005; Biol Psychiatry 57:1313-1323; Thapar et al., 2005; Hum Mol Genet 14 Spec No. 2:R275-R282]. As a follow up to a pilot study [see Castellanos et al., 1998; Mol Psychiatry 3:431-434] consisting of 41 probands and 56 controls which found no significant association between the DRD4 7-repeat allele in exon 3 and ADHD, a greatly expanded study sample (cases n = 166 and controls n = 282) and long term follow-up (n = 107, baseline mean age n = 9, follow-up mean age of n = 15) prompted reexamination of this gene. The DRD4 7-repeat allele was significantly more frequent in ADHD cases than controls (OR = 1.2; P = 0.028). Further, within the ADHD group, the 7-repeat allele was associated with better cognitive performance (measured by the WISC-III) (P = 0.013-0.07) as well as a trend for association with better long-term outcome. This provides further evidence of the role of the DRD4 7-repeat allele in the etiology of ADHD and suggests that this allele may be associated with a more benign form of the disorder.
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 DRD4 and DAT1 polymorphisms with childhood ADHD is inconsistent, with some candidate-gene studies finding associations and a case-control study finding none.
“For example, multiple candidate-gene association studies have indicated that polymorphisms in DRD4 and DAT1 are associated with cADHD (Brookes K. et al., 2006; Gornick et al., 2007), while results from a case-control study did not find any association between these two genes and ADHD (Johansson et al., 2008).”
From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Gornick et al., 2007
The paper reports a significant association between the DRD4 7-repeat allele and childhood ADHD (opening summary; Discussion). It does not report a DAT1 association. The case-control study finding no association is attributed to Johansson et al. in the citing sentence, not to Gornick et al. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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
The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions
Gottesman, I. I., & Gould, T. D. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.4.636 · Cited by 5,615 · see citing works
A Children's Global Assessment Scale (CGAS)
Shaffer, D. (1983) · Archives of General Psychiatry · doi:10.1001/archpsyc.1983.01790100074010 · Cited by 3,716 · 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
Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes
Castellanos, F. X., & Tannock, R. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn896 · Cited by 1,827 · see citing works
Self-citationNormative data on Revised Conners Parent and Teacher Rating Scales
Goyette, C. H., Conners, C. K., & Ulrich, R. F. (1978) · Research on Child and Adolescent Psychopathology · doi:10.1007/bf00919127 · Cited by 1,712 · see citing works
Achenbach, T. M., & EDELBROCK, C. S. (1981) · Monographs of the Society for Research in Child Development · doi:10.2307/1165983 · Cited by 1,690 · see citing works
Castellanos, F. X. (2002) · JAMA · doi:10.1001/jama.288.14.1740 · Cited by 1,646 · see citing works
Self-citationPedigree disequilibrium tests for multilocus haplotypes.
Dudbridge, F. (2003) · Genetic Epidemiology · doi:10.1002/gepi.10252 · Cited by 1,135 · see citing works
Diagnostic Interview for Children and Adolescents (DICA)
Reich, W. (2000) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200001000-00017 · Cited by 818 · see citing works
Neurobiology of attention-deficit hyperactivity disorder
Faraone, S. V., & Biederman, J. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00240-6 · Cited by 811 · see citing works
Shaw, P., Lerch, J., Greenstein, D., Sharp, W., Clasen, L., Evans, A., Giedd, J., Castellanos, F. X., & Rapoport, J. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.5.540 · Cited by 703 · see citing works
Self-citationDopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder.
LaHoste, G. J., Swanson, J. M., Wigal, S. B., Glabe, C. G., Wigal, T. L., King, N., & Kennedy, J. L. (1996) · PubMed · Cited by 678 · see citing works
Achenbach, T. M., Howell, C. T., Quay, H. C., Conners, C. K., & Bates, J. E. (1991) · Monographs of the Society for Research in Child Development · doi:10.2307/1166156 · Cited by 571 · see citing works
Evidence of positive selection acting at the human dopamine receptor D4 gene locus
Ding, Y. C., Chi, H. C., Grady, D., Morishima, A., Kidd, J., Kidd, K., Flodman, P., Spence, M., Schuck, S., Swanson, J., et al. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.012464099 · Cited by 506 · see citing works
Swanson, J. M., Sunohara, G., Kennedy, J. L., Regino, R., Fineberg, E. S., Wigal, T. L., Lerner, M., Williams, L., LaHoste, G. J., & Wigal, S. B. (1998) · Molecular Psychiatry · doi:10.1038/sj.mp.4000354 · Cited by 375 · see citing works
A genomewide scan for loci involved in attention-deficit/hyperactivity disorder.
Fisher, S. E., Francks, C., McCracken, J. T., McGough, J. J., Marlow, A., MacPhie, I. L., Newbury, D., Crawford, L., Palmer, C. G. S., Woodward, J., et al. (2002) · American Journal of Human Genetics · doi:10.1086/340112 · Cited by 318 · see citing works
Conners' Teacher Rating Scale for use in drug studies with children ? An empirical study
WERRY, J. S., Sprague, R. L., & Cohen, M. N. (1976) · Research on Child and Adolescent Psychopathology · doi:10.1007/bf00916752 · Cited by 268 · see citing works
Swanson, J., Oosterlaan, J., Murias, M., Schuck, S., Flodman, P., Spence, M. A., Wasdell, M., Ding, Y., Chi, H.-C., Smith, M., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.080070897 · Cited by 267 · see citing works
The genetics of attention deficit hyperactivity disorder
Thapar, A., O’Donovan, M. C., & Owen, M. J. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi263 · Cited by 235 · see citing works
Dopamine D4 Gene 7-Repeat Allele and Attention Deficit Hyperactivity Disorder
Faraone, S. V., Biederman, J., Weiffenbach, B., Keith, T. P., Chu, M. P., Weaver, A., Spencer, T. J., Wilens, T. E., Frazier, J. A., Cleves, M. A., et al. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.5.768 · Cited by 234 · see citing works
Ogdie, M. N., Macphie, I. L., Minassian, S. L., Yang, M., Fisher, S. E., Francks, C., Cantor, R. M., McCracken, J. T., McGough, J. J., Nelson, S. F., et al. (2003) · The American Journal of Human Genetics · doi:10.1086/375139 · Cited by 220 · see citing works
Smalley, S., Bailey, J. N., Palmer, C. G. S., Cantwell, D. P., McGough, J. J., Del’Homme, M., Asarnow, J. R., Woodward, J. A., Ramsey, C., & Nelson, S. F. (1998) · Molecular Psychiatry · doi:10.1038/sj.mp.4000457 · Cited by 218 · see citing works
Langley, K., Marshall, L., van den Bree, M. V. D., Thomas, H., Owen, M., O'Donovan, M., & Thapar, A. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.1.133 · Cited by 206 · see citing works
Molecular genetic studies of ADHD: 1991 to 2004
Bobb, A. J., Castellanos, F. X., Addington, A. M., & Rapoport, J. L. (2004) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30086 · Cited by 188 · see citing works
Self-citationRoman, T., Schmitz, M. D., Polanczyk, G. V., Eizirik, M., Rohde, L. A., & Hutz, M. H. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1408 · Cited by 171 · see citing works
Dysfunctional attention in autistic savants
Casey, B. J., Gordon, C. T., Mannheim, G. B., & Rumsey, J. M. (1993) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/01688639308402609 · Cited by 164 · see citing works
Castellanos, F. X., Lau, E. K., Tayebi, N., Lee, P., Long, R. E., Giedd, J. N., Sharp, W. S., Marsh, W., Walter, J. M., Hamburger, S. D., et al. (1998) · Molecular Psychiatry · doi:10.1038/sj.mp.4000430 · Cited by 162 · see citing works
Self-citationTahir, E., Yazgan, Y., Çırakoğlu, B., Ozbay, F., Waldman, I. D., & Asherson, P. J. (2000) · Molecular Psychiatry · doi:10.1038/sj.mp.4000744 · Cited by 156 · see citing works
Holmes, J., Payton, A., Barrett, J. H., Hever, T., Fitzpatrick, H., Trumper, A., Harrington, R., McGuffin, P., Owen, M. J., Ollier, W., et al. (2000) · Molecular Psychiatry · doi:10.1038/sj.mp.4000751 · Cited by 146 · see citing works
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 · see citing works
Linkage of the Dopamine D4 Receptor Gene and Attention-Deficit/Hyperactivity Disorder
Sunohara, G., Roberts, W., MALONE, M. A., Schachar, R. J., Tannock, R., Basile, V. S., Wigal, T. L., Wigal, S. B., Schuck, S. E. B., Moriarty, J., et al. (2000) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200012000-00017 · Cited by 108 · 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
Association of DRD4 in children with ADHD and comorbid conduct problems
Holmes, J., Payton, A., Barrett, J. H., Harrington, R., McGuffin, P., Owen, M. J., Ollier, W., Worthington, J., Gill, M., Kirley, A., et al. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10149 · Cited by 101 · see citing works
Furlong, R. A., Ho, L. W., Rubinsztein, J. S., Walsh, C., Paykel, E. S., & Rubinsztein, D. C. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19990820)88:4 · Cited by 100 · see citing works
Mill, J. S., Curran, S. R., Kent, L., Richards, S., Gould, A., Virdee, V., Huckett, L., Sharp, J., Batten, C., Fernando, S., et al. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000881 · Cited by 74 · see citing works
Arcos-Burgos, M., Castellanos, F., Konecki, D., Lopera, F., Pineda, D., Palacio, J., Rapoport, J., Berg, K., Bailey-Wilson, J., & Muenke, M. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001396 · Cited by 68 · see citing works
Self-citationCurran, S. R., Mill, J. S., Sham, P. C., Rijsdijk, F. V., Marusic, K., Taylor, E., & Asherson, P. J. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1366 · Cited by 52 · see citing works
Bhaduri, N., Das, M., Sinha, S., Chattopadhyay, A., Gangopadhyay, P., Chaudhuri, K., Singh, M., & Mukhopadhyay, K. (2006) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30225 · Cited by 41 · see citing works
Marino, C., Giorda, R., Vanzin, L., Molteni, M., Lorusso, M. L., Nobile, M., Baschirotto, C., Alda, M., & Battaglia, M. (2003) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-003-0332-4 · Cited by 35 · see citing works
Donnelly, S. L., Wolpert, C. M., Menold, M. M., Bass, M. P., Gilbert, J. R., Cuccaro, M. L., Delong, G. R., & Pericak-Vance, M. A. (2000) · American Journal of Medical Genetics · doi:10.1002/1096-8628(20000612)96:3
Flagged first, then by citations
Research works printed but not linked: 2
- American Psychiatric Association. 1994. American Psychiatric Association: diagnostic and statistical manual of mental disorders, Fourth Edition. Washington D.C.: American Psychiatric Association.
- Hawi Z, McCarron M, Kirley A, Daly G, Fitzgerald M, Gill M. 2000. No association of the dopamine DRD4 receptor (DRD4) gene polymorphism with attention deficit hyperactivity disorder (ADHD) in the Irish population. Am J Med Genet 96(3):268-272.
Cited by
Sorted by citations
Candidate gene studies of ADHD: a meta-analytic review
Gizer, I. R., Ficks, C., & Waldman, I. D. (2009) · Human Genetics · doi:10.1007/s00439-009-0694-x · Cited by 1,020 · see citing works
A 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
“…multiple candidate-gene association studies have indicated that polymorphisms in DRD4 and DAT1 are associated with cADHD (Brookes K. et al., 2006; Gornick et al., 2007), while results from a case-control study did not find any association between these two genes and ADHD (Johansson et al., 2008).”
ResultShaw, 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
Self-citationTestosterone exposure, dopaminergic reward, and sensation-seeking in young men
Campbell, B. C., Dreber, A., Apicella, C. L., Eisenberg, D. T. A., Gray, P. B., Little, A. C., Garcia, J. R., Zamore, R. S., & Lum, J. K. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.12.011 · Cited by 133 · 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
Gonon, F., Bezard, E., & Boraud, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014618 · Cited by 71 · see citing works
ADHD candidate gene (DRD4 exon III) affects inhibitory control in a healthy sample
Krämer, U. M., Rojo, N., Schüle, R., Cunillera, T., Schöls, L., Marco-Pallarés, J., Cucurell, D., Camara, E., Rodriguez-Fornells, A., & Münte, T. F. (2009) · BMC Neuroscience · doi:10.1186/1471-2202-10-150 · Cited by 42 · see citing works
Sánchez‐Mora, C., Richarte, V., Garcia‐Martínez, I., Pagerols, M., Corrales, M., Bosch, R., Vidal, R., Viladevall, L., Casas, M., Cormand, B., et al. (2015) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32340 · Cited by 23 · see citing works
- Authors
- Gornick, M. C., Addington, A., Shaw, P., Bobb, A. J., Sharp, W., Greenstein, D., Arepalli, S., Castellanos, F. X., & Rapoport, J. L.
- Affiliations
- National Institutes of Health (US)
- New York University (US)
- Corresponding author
- Addington, Anjene
- Venue
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2006-12-14
- Volume
- 144B
- Issue
- 3
- Pages
- 379-382
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W2085197269
- Cited by
- 77
- References
- 40
- Citations by year
- 2024: 5 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 6 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 6 · 2013: 1 · 2012: 8
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- public-domain
- onlinelibrary.wiley.com/termsAndConditions#vor (vor)
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, public-domain)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- attention deficit hyperactivity disorder, dopamine D4 receptor, 11p15.5, genetic association, children, cognitive performance, long-term outcomes, ADHD etiology
- MeSH terms
- Adolescent, Adult, Alleles, Attention Deficit Disorder with Hyperactivity, Child, Family, Gene Frequency, Humans, Genetic Linkage, Case-Control Studies, Minisatellite Repeats, Receptors, Dopamine D4
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
