Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: Heterogeneity owing to diagnostic subtype and severity
Open accessAbstract
Attention-deficit hyperactivity disorder (ADHD) affects approximately 3%-5% of children in the United States. In the current psychiatric nomenclature, ADHD comprises three subtypes: inattentive, hyperactive-impulsive, and combined. In this study, we used four analytic strategies to examine the association and linkage of the dopamine transporter gene (DAT1) and ADHD. Our sample included 122 children referred to psychiatric clinics for behavioral and learning problems that included but were not limited to ADHD, as well as their parents and siblings. Within-family analyses of linkage disequilibrium, using the transmission disequilibrium test (TDT), confirmed the 480-bp allele as the high-risk allele. In between-family association analyses, levels of hyperactive-impulsive symptoms but not inattentive symptoms were related to the number of DAT1 high-risk alleles. Siblings discordant for the number of DAT1 high-risk alleles differed markedly in their levels of both hyperactive-impulsive and inattentive symptoms, such that the sibling with the higher number of high-risk alleles had much higher symptom levels. Within-family analyses of linkage disequilibrium, using the TDT, suggested association and linkage of ADHD with DAT1 and that this relation was especially strong with the combined but not the inattentive subtype. The relation of DAT1 to ADHD increased monotonically, from low to medium to high levels of symptom severity. Our results replicate and extend previous findings of the…
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Dopaminergic hypofunction is thought to play an important role in the etiology of ADHD.
“The neurobiological underpinnings of ADHD are not well established; however, dopaminergic hypofunction is thought to play an important role in the etiology of this disorder (Hynd et al., 1993; Gill et al., 1997; Waldman et al., 1998; Russell, 2003; Bush et al., 2005; Sagvolden et al., 2005b).”
From The Effects of Methylphenidate on Goal-directed Behavior in a Rat Model of ADHD (2015) · cites this paper as Waldman et al., 1998
The dopamine transporter gene DAT1 has been linked to ADHD and with violent behavior and delinquency in adolescents and young adults.
“Dopamine transporter gene DAT1 has also been linked to ADHD (Waldman et al., 1998), as well as with violent behavior and delinquency in adolescents and young adults (Guo et al., 2008).”
From Human Aggression Across the Lifespan (2011) · cites this paper as Waldman et al., 1998
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“Dopamine transporter gene DAT1 has also been linked to ADHD (Waldman et al., 1998), as well as with violent behavior and delinquency in adolescents and young adults (Guo et al., 2008).”
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- Authors
- Waldman, I. D., Rowe, D. C., Abramowitz, A., Kozel, S. T., Mohr, J. H., Sherman, S. L., Cleveland, H. H., Sanders, M. L., Gard, J. M. C., & Stever, C.
- Affiliations
- Emory University (US)
- University of Arizona (US)
- Corresponding author
- Waldman, I.D.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 1998-12
- Volume
- 63
- Issue
- 6
- Pages
- 1767-1776
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1377649
- OpenAlex
- W2096943304
- Cited by
- 462
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 9 · 2018: 4 · 2017: 12 · 2016: 2 · 2015: 16 · 2014: 18 · 2013: 10 · 2012: 9
- FWCI
- 19.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Harry Frank Guggenheim Foundation
- School of Medicine, Emory University
- 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, dopamine transporter gene, DAT1, genetic linkage, candidate gene association, ADHD subtypes, hyperactive-impulsive symptoms, inattentive symptoms, symptom severity, transmission disequilibrium test, linkage disequilibrium, children
- MeSH terms
- Alleles, Attention Deficit Disorder with Hyperactivity, Behavioral Symptoms, Carrier Proteins, Child, Diseases in Twins, Ethnicity, Female, Genes, Dominant, Genes, Recessive, Humans, Learning Disabilities, Genetic Linkage, Male, Membrane Glycoproteins, Models, Genetic, Nerve Tissue Proteins, Nuclear Family, Phenotype, Psychiatric Status Rating Scales, Linkage Disequilibrium, Linear Models, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins
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