ArticleAmerican journal of human genetics2004
The genetic architecture of selection at the human dopamine receptor D4 (DRD4) gene locus.
Article in American journal of human genetics, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 4 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
127 citing papers in PubMed, 4 syntheses or guidelines pooled it, 402 citations in OpenAlex.
- Dopaminergic Genetic Variation in Young Adolescents: Associations with Sensation-Seeking.Research on child and adolescent psychopathology · 2021Pooled it
- Parsing out the role of dopamine D4 receptor gene (DRD4) on alcohol-related phenotypes: A meta-analysis and systematic review.Addiction biology · 2020Pooled it
- Brain imaging genetics in ADHD and beyond - Mapping pathways from gene to disorder at different levels of complexity.Neuroscience and biobehavioral reviews · 2017Pooled it
- ADHD and the DRD4 exon III 7-repeat polymorphism: an international meta-analysis.Social cognitive and affective neuroscience · 2010Pooled it
- Dopaminergic genetic variation moderates the effect of nicotine on cigarette reward.Psychopharmacology · 2016Trial
- Effects of nicotine deprivation and replacement on BOLD-fMRI response to smoking cues as a function of DRD4 VNTR genotype.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2014Trial
- The DRD4 exon III VNTR, bupropion, and associations with prospective abstinence.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2013Trial
- Religion priming differentially increases prosocial behavior among variants of the dopamine D4 receptor (DRD4) gene.Social cognitive and affective neuroscience · 2013Trial
- Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation.The pharmacogenomics journal · 2012Trial
- Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter volumes in a sample of subjects with attention deficit hyperactivity disorder, their unaffected siblings, and controls.Molecular psychiatry · 2005Trial
- Dopaminergic polymorphisms associated with self-report measures of human altruism: a fresh phenotype for the dopamine D4 receptor.Molecular psychiatry · 2005Trial
- Evolutionary Balancing of Genetic Consequence and Innovation in Mammals Through Variable Number Tandem Repeats.Genome biology and evolution · 2026Review
- Developmental cascades from early childhood attachment security to adolescent level of personality functioning among high-risk youth.Development and psychopathology · 2025Article
- The Attention-Deficit/Hyperactivity Disorder-Associated DRD4 7R Allele Predicts Household Economic Status but Not Nutritional Status in Northern Kenyan Rendille Children.American journal of human biology : the official journal of the Human Biology Council · 2025Article
- Genes, culture, and neural sensitivity to norm violations: a DRD4 × culture interaction study.Social cognitive and affective neuroscience · 2025Article
- Humanized dopamine DJournal of neuroscience research · 2024Review
- Significant Functional Differences Between Dopamine DMolecular neurobiology · 2023Article
- Art Value Creation and Destruction.Integrative psychological & behavioral science · 2023Article
- The effect of the 7R allele at the DRD4 locus on risk tolerance is independent of background risk in Senegalese fishermen.Scientific reports · 2023Article
- Prevalence of Common Alleles of Some Stress Resilience Genes among Adolescents Born in Different Periods Relative to the Socioeconomic Crisis of the 1990s in Russia.Current issues in molecular biology · 2022Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Associations of the seven-repeat (7R) allele of the human dopamine receptor D4 (DRD4) gene with both the personality trait of novelty seeking and attention deficit/hyperactivity disorder have been reported. Recently, on the basis of the unusual DNA sequence organization of the DRD4 7R 48-bp tandem repeat (VNTR), we proposed that the 7R allele originated as a rare mutational event that increased to high frequency by positive selection. We now have resequenced the entire DRD4 locus from 103 individuals homozygous for 2R, 4R, or 7R variants of the VNTR, a method developed to directly estimate haplotype diversity. DNA from individuals of African, European, Asian, North and South American, and Pacific Island ancestry were used. 4R/4R homozygotes exhibit little linkage disequilibrium (LD) over the region examined, with more polymorphisms observed in DNA samples from African individuals. In contrast, the evidence for strong LD surrounding the 7R allele is dramatic, with all 7R/7R individuals (including those from Africa) exhibiting the same alleles at most polymorphic sites. By intra-allelic comparison at 18 high-heterozygosity sites spanning the locus, we estimate that the 7R allele arose prior to the upper Paleolithic era (approximately 40000-50000 years ago). Further, the pattern of recombination at these polymorphic sites is the pattern expected for selection acting at the 7R VNTR itself, rather than at an adjacent site. We propose a model for selection at the DRD4 locus consistent with these observed LD patterns and with the known biochemical and physiological differences between receptor variants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.