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Cited by 587Neurotransmitter Receptor Influence on BehaviorGenetic Associations and EpidemiologySchizophrenia research and treatment

The Dopamine D2 Receptor Locus as a Modifying Gene in Neuropsychiatric Disorders

Comings, David E.·1991·JAMA: The Journal of the American Medical Association
DOI 10.1001/jama.1991.03470130073032
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Abstract

OBJECTIVE: --The A1 allele of the Taq I polymorphism of the dopamine D2 receptor (DRD2) gene has been earlier reported to occur in 69% of alcoholics, compared with 20% of controls. Other research has reported no significant difference in the prevalence of the A1 allele in alcoholics vs controls and no evidence that the DRD2 gene was linked to alcoholism. We hypothesized that these seemingly conflicting results might be because increases in the prevalence of the A1 allele may not be specific to alcoholism. Thus, we examined other disorders frequently associated with alcoholism or those believed to involve defects in dopaminergic neurotransmission. DESIGN: --Case comparison study. To minimize the effect of racial differences in gene frequencies, the study was restricted to non-Hispanic whites. SETTING: --Ambulatory and hospitalized patients. RESULTS: --Among all known controls (n = 314), 77 (24.5%) carried the A1 allele. Of the 69 controls known not to be alcoholics, 10 (14.5%) carried the A1 allele. The prevalence of the A1 allele was significantly increased in patients with Tourette's syndrome (44.9%, n = 147), attention deficit hyperactivity disorder (46.2%, n = 104), autism (54.5%, n = 33), alcoholism (42.3%, n = 104), and posttraumatic stress disorder (45.7%, n = 35). After correction for multiple comparisons (requiring P less than .0009 for significance), all remained significant except posttraumatic stress disorder. The prevalence of the A1 allele was not significantly increased in patients with depression, panic attacks, Parkinson's disease, or obesity. The prevalence of the A1 allele in drug addiction and schizophrenia was only significant when compared with that of controls who were not alcoholics, and no correction was made for multiple comparisons. CONCLUSION: --These results suggest the A1 allele of the DRD2 gene is associated with a number of behavior disorders in which it may act as a modifying gene rather than as the primary etiological agent.

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Authors
Comings, D. E.
Affiliations
City Of Hope National Medical Center (US)
Corresponding author
Comings, David E.
ORCID
Comings, David E.
Venue
JAMA: The Journal of the American Medical Association
Publisher
American Medical Association (AMA)
Published
1991-10-02
Volume
266
Issue
13
Pages
1793
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.1991.03470130073032
OpenAlex
W2112696084
Cited by
587
References
58
Citations by year
2026: 1 · 2025: 3 · 2024: 1 · 2023: 9 · 2022: 10 · 2021: 7 · 2020: 4 · 2019: 9 · 2018: 11 · 2017: 7 · 2016: 13 · 2015: 15 · 2014: 20 · 2013: 16 · 2012: 13
FWCI
10.80
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1r01mh045908-01)
  • National Institute of Mental Health (MH41960, MH45908)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
dopamine D2 receptor, DRD2 gene, TaqI polymorphism, A1 allele, alcoholism, Tourette syndrome, attention deficit hyperactivity disorder, autism spectrum disorder, post-traumatic stress disorder, neuropsychiatric disorders, dopamine signaling, modifying genes, genetic association
MeSH terms
Alcoholism, Alleles, Attention Deficit Disorder with Hyperactivity, Autistic Disorder, Mental Disorders, Brain Diseases, Chromosome Aberrations, DNA, DNA-Directed DNA Polymerase, Genotype, Tourette Syndrome, Humans, Parkinson Disease, Receptors, Dopamine, Receptors, Dopamine D2, Taq Polymerase, Substance-Related Disorders, Chromosome Disorders

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