rs1800955
badMag 3.0This is a 2kb upstream variant variant in the DRD4 gene.
Key Literature Trait Associations
Internet addiction disorder
A genome-wide association study of internet addiction disorder (Haghighatfard et al., 2023) identified rs1800955 in the DRD4 promoter region as a significant locus with OR=1.26 and p=2×10⁻⁸ in an Iranian cohort of 16,520 cases and 18,000 controls. This was described as the first GWAS of internet addiction and identified substantial shared genetic architecture with neurodevelopmental psychiatric disorders including autism spectrum disorder, bipolar disorder, and schizophrenia. The dopaminergic pathway implication is biologically plausible given DRD4's role in reward processing and impulse control. This finding requires replication in independent cohorts before firm conclusions can be drawn.
Novelty Seeking
rs1800955 (-521C/T) lies in the promoter of the dopamine D4 receptor gene DRD4, where the T allele reduces transcriptional efficiency by approximately 40% relative to C. The C allele (higher receptor expression) was associated with elevated novelty-seeking scores on the Temperament and Character Inventory, with the CC genotype showing the highest scores and TT the lowest. A subsequent meta-analysis confirmed a modest but replicable association, with the C allele accounting for roughly 2% of phenotypic variance.
Cigarette smoking
Two independent candidate-gene studies have reported associations between the DRD4 rs1800955 C allele and cigarette smoking. A Mexican study (Pérez-Rubio et al., 2017) of 1,595 participants found the C allele associated with heavy smoking (p=2.34×10⁻³) and light smoking (p=1.13×10⁻³) versus non-smoking, with CC homozygotes showing stronger effects. An Egyptian university cohort (Aboelsaad et al., 2022) replicated the C allele association in both heavy and light smokers versus non-smokers. Both studies are relatively small candidate-gene designs and neither reaches genome-wide significance; larger replication is needed.
Attention deficit hyperactivity disorder
rs1800955 has been implicated in ADHD primarily through haplotype analyses rather than as an independent risk variant. Two family-based studies from Eastern India found significant preferential transmission of a DRD4 VNTR-7R/rs1800955-T haplotype to ADHD probands (p=0.02 and p=0.008), with the effect more pronounced in males. A study by Bellgrove et al. (2005) found the -521 A allele (note: alternate allele nomenclature) associated with greater sustained attention impairment in 54 ADHD probands. However, a Chinese longitudinal study found no significant association with ADHD persistence into adulthood. Evidence is restricted to small candidate-gene studies and haplotype effects; the variant has not reached genome-wide significance for ADHD in large meta-analyses.
Extraversion
The DRD4 -521 C/T promoter polymorphism has been associated with extraversion and social behavior in two small candidate-gene studies. A Russian sample of 220 healthy subjects found significant associations between the -521 genotype and both extraversion (EPI scale, P=0.0016) and Social Introversion (MMPI scale, P=0.0085), with the T allele linked to reduced social activity given its lower transcription rate. An African American study reported a significant three-way interaction of gender × DRD4 -616 × DRD4 -521 genotypes predicting extraversion scores, primarily driven by females (P=0.01). These findings are based on small samples and require replication.
▶ClinVar annotation
▶Research that mentions this SNP (9)
▶Association of the matrix metalloproteinase 3 (MMP3) single nucleotide polymorphisms with tendinopathies: case-control study in high-level athletesCase reportNina Briški et al.(2021)· International Orthopaedics
This is a Turkish-language personalized nutrigenetics and epigenetics coaching report for individual Mehmet Efe Yildirim (Report No. 1332, dated 2023-11-21). The report analyzes the individual's genetic polymorphisms related to nutritional metabolism, food sensitivities, detoxification pathways, and other health-related traits, providing personalized dietary and lifestyle recommendations based on cited scientific literature. This is a direct-to-consumer genetic test report, not a peer-reviewed research study.
▶Association between catechol‐O‐methyl transferase gene polymorphisms and fibromyalgia in a Korean population: A case–control studyAssociationN=426Park DJ et al.(2016)· European Journal of Pain
This international doctoral thesis examined gene-physical activity interactions in fibromyalgia through six studies analyzing 64 SNPs across 34 candidate genes in Spanish women. The case-control study (314 fibromyalgia cases vs. 112 controls) identified associations of rs841 (GCH1), rs1799971 (OPRM1), and rs2097903 (COMT) with fibromyalgia susceptibility (p=0.04, p=0.02, and p=0.04 respectively). Cross-sectional studies (n=274-276 fibromyalgia patients) found that SCN9A rs4453709 and other genetic polymorphisms interacted with physical activity to influence pain, fatigue, and resilience outcomes.
▶The relationship between polymorphisms of BDNFOS and BDNF genes and heroin addiction in the Han Chinese populationReviewTianbo Jin et al.(2016)· The Journal of Gene Medicine
This review examines neurogenetic and neuropharmacological correlates of opioid use disorder (OUD) with emphasis on ancestry-specific genetic risk profiles. The paper identifies multiple genes involved in the reward pathway (DRD2, DRD3, DRD4, OPRM1, OPRK1, OPRD1, BDNF, NRXN3, COMT, SLC6A4, KCNC1, KCNG2) and their variants associated with OUD susceptibility and treatment response across different ethnic populations, highlighting critical research disparities where African Americans and Hispanics have been underrepresented in genetic association studies.
▶Association of RANBP1 haplotype with smooth pursuit eye movement abnormalityReviewHyun Sub Cheong et al.(2011)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
This comprehensive review examines the genomics of schizophrenia and pharmacogenomics of antipsychotic drugs, synthesizing evidence on over 200 genes associated with psychotic disorders. The authors discuss five categories of genes relevant to antipsychotic response: disease-associated genes, mechanism-of-action genes, drug metabolism genes (particularly CYP2D6, CYP2C19, CYP2C9, CYP3A4), drug transporter genes, and pleiotropic genes. The review details pharmacogenomic profiles of 20+ antipsychotic drugs and demonstrates significant ethnic and interindividual variation in drug metabolism phenotypes, with examples including CYP2D6 extensive metabolizers (55.71% of population), intermediate metabolizers (34.7%), poor metabolizers (2.28%), and ultra-rapid metabolizers (7.31%).
▶Familiality and molecular genetics of attention networks in ADHDAssociationN=1,833Kerstin Konrad et al.(2010)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
A Hungarian doctoral dissertation examining psychogenetic endophenotypes through multiple candidate gene association studies. Investigated dopaminergic and serotonergic polymorphisms (DRD2, DRD4, COMT, GDNF, HTR1A, HTR1B, SLC6A4) in relation to personality dimensions (impulsivity, anxiety, depression), flow susceptibility, hypnotizability, cognitive reaction time, and longevity. Key findings include associations between GDNF rs3812047 and rs3096140 with anxiety measures (p=0.0007, p=0.0014), COMT Val158Met with hypnotizability, and DRD4 VNTR 7-repeat with reaction time.
▶Significant association between the C(−1019)G functional polymorphism of the HTR1A gene and impulsivityAssociationN=1,862Anita Benko et al.(2010)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
This Hungarian dissertation examined psychogenetic endophenotypes in healthy young adults (N~1800+), investigating associations between dopaminergic and serotonergic genetic polymorphisms and psychological traits including impulsivity, mood dimensions, flow susceptibility, hypnotizability, and cognitive performance. Key findings included significant associations between DRD4 VNTR 7-repeat allele and lower impulsivity (p=0.006), COMT Val/Met (rs4680) and impulse control (p=0.047), HTR1B 1997 AG (rs13212041) and impulsivity (p=0.003-0.004), GDNF variants and anxiety, and notably, a population frequency increase in DRD4 7-repeat allele carriers with advancing age suggesting possible survival advantage.
▶Candidate gene studies of ADHD: a meta-analytic reviewMeta-analysisIan R. Gizer et al.(2009)· Human Genetics
Meta-analytic review of candidate gene studies for childhood ADHD examining 19 genes. Significant associations identified for DAT1 (3' UTR VNTR: OR=1.12, p=0.028; rs27072: OR=1.20, p=0.006), DRD4 (exon 3 VNTR: OR=1.33, p=0.00007; rs1800955: OR=1.21, p=0.007), DRD5, 5HTT, HTR1B (rs6296: OR=1.11, p=0.010), and SNAP25 (rs3746544: OR=1.15, p=0.030).
▶Influence of NOS1 on Verbal Intelligence and Working Memory in Both Patients With Schizophrenia and Healthy Control SubjectsReviewGary Donohoe et al.(2009)· Archives of General Psychiatry
This comprehensive review synthesizes genomic and pharmacogenomic research in schizophrenia, discussing over 200 candidate genes associated with psychotic disorders, genetic mechanisms including copy number variants and microRNA alterations, and pharmacogenomic factors affecting antipsychotic efficacy and safety. Key genes covered include dopamine receptors (DRD1-5), dysbindin (DTNBP1), DISC1, neurotrophic factors, and metabolic enzymes such as CYP2D6, CYP3A4, and COMT, with emphasis on genotype-phenotype correlations in antipsychotic response and side effects.
▶A Linkage Disequilibrium between Genes at the Serine Protease Inhibitor Gene Cluster on Chromosome 14q32.1 Is Associated with Wegener's GranulomatosisAssociationN=350Stefan Borgmann et al.(2001)· Clinical Immunology
This doctoral thesis conducted multiple candidate gene association studies in 274-426 southern Spanish women with fibromyalgia to investigate gene-physical activity/sedentary behavior interactions with pain, fatigue, and resilience. Study III identified rs841 (GCH1) GG genotype (OR=0.61, p=0.04) and rs2097903 (COMT) AT/TT genotypes (OR=1.66, p=0.04) associated with fibromyalgia susceptibility, and confirmed rs1799971 (OPRM1) GG genotype (OR=0.58, p=0.02) confers genetic risk. Study IV found rs6311/rs6313 (HTR2A) polymorphisms individually associated with algometer pain score, and gene-sedentary behavior interactions involving rs4680/rs165599 (COMT), rs1383914 (ADRA1A), rs12994338/rs4453709 (SCN9A), and rs6860 (CHMP1A) significantly associated with pain outcomes. SCN9A emerged as most robust gene for fibromyalgia phenotype.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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