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- Data Summary
Gene Report
Approved Symbol | DRD4 |
---|---|
Approved Name | dopamine receptor D4 |
Location | 11p15.5 |
Position | chr11:637293-640706, + |
External Links |
HGNC: 3025 Entrez Gene: 1815 Ensembl: ENSG00000069696 UCSC: uc001lqp.1 |
No. of Studies | 67 (significant: 49; non-significant: 18; trend: 0) |
Source | Literature-origin; Mapped by literature SNP |
Reference | Statistical Values/Author Comments | Result of Statistical Analysis |
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Spencer, T. J., 2012 | the gene frequencies of each of the gene polymorphisms assessed did not differ between the ADHD and control groups. | Non-significant |
Carpentier, P. J., 2012 | No significant association was found. | Non-significant |
Sanchez-Mora C, 2011 | chi-square test P-value>0.05 for haplotype frequencies, showed no association in any of the four separate cohorts; meta-analysis: P-value=0.01, OR=0.78 showed an under representation of the S-4R allelic combination in the ADHD sample; P-value=0.04, OR=0.73 in females; S-4R P-value=0.01, OR=0.75; L-4R P-value=0.02, OR=1.29, showed an increased frequency of carriers of the L-4R risk haplotype in addition to an under-representation of the S-4R allelic combination in this clinical dataset. P-value=3.04e-05, OR=1.66; P-value=2.66e-05, OR=1.74 of DRD4 L-4R and SLC6A3 9R-6R increased the risk for ADHD in both the ADHD sample as a whole and in the combined clinical subtype respectively which suggested additive effects of the DRD4 risk haplotype and the SLC6A3 gene | Significant |
Nyman ES, 2007 | No evidence of association was seen. | Non-significant |
Johansson S, 2008 | no association between ADHD and the DRD4 polymorphism | Non-significant |
Lasky-Su J, 2007 | One of the four SNPswas associatedwith the quantitative phenotypes generated fromthe ADHDsymptoms. | Significant |
Yang JW, 2008 | there was a significant association between the -521 C/T SNP and ADHD in Korean boys | Significant |
Oades RD, 2008 | 1 SNP and 1 polymorphism showed significant association | Significant |
Niederhofer H, 2008 | they did not observe an association of ADHD with DRD4 polymorphism neither by the haplotype relative risk (HRR) method nor by the transmission disequilibrium test (TdT) method. | Non-significant |
Johnson KA, 2008 | a significant association between possession of the 7-repeat allele and diagnosis | Significant |
Langley K, 2009 | significant association between the DRD4 48 bp VNTR 7-repeat allele and 'persistent ADHD'. | Significant |
Nikolaidis A, 2010 | the Caucasian group showed a positive relationship between ADHD and the DRD4 7R allele; the Middle Eastern group showed a negative relationship between ADHD and the DRD4 7R allele; The South American group also demonstrated a positive relationship between ADHD and the DRD4 7R allele; The Asian group demonstrated a positive relationship between the DRD4 2R allele and ADHD, but the results were insignificant | Significant |
Smith TF, 2010 | consistent with previous meta-analytic work, the DRD4 7R allele was associated with AD/HD across studies. Combined type individuals within the AD/HD sample was associated with a significant increase in the magnitude of association between the DRD4 7R allele and AD/HD. | Significant |
Gabriela ML, 2009 | genotype analysis P-value=0.19; allelic analysis P-value=0.18 | TDT P-value=0.59. No significant differences between groups of comparison. | Non-significant |
Gizer IR, 2009 | The present study provides significant evidence suggesting an association between childhood ADHD and this gene. | Significant |
Das M, 2011 | minimum UNPHASED P-value=0.29 for haplotype frequencies in the case-control analysis showed no significant difference; minimum ETDT P-value=0.02, X2(1df)=5.54, RR=5.18e+008, which showed significant over transmission of the 7R-T haplotypes from parents | Significant |
Tovo-Rodrigues L, 2011 | Findings in this study suggest an association between ADHD and DRD4 rare variants. | Significant |
Ilott NE, 2010 | 1 SNP showed modest, nominally significant association in the AT and AW tests at age 3 | Significant |
Bidwell LC, 2011 | In the current study, the DRD4 VNTR 4-repeat allele was associated with increased ADHD symptomatology. | Significant |
Holmes J, 2000 | A significant increase in the DRD4 7 repeat allele amongst ADHD probands and their parents was observed, compared to ethnically matched controls. However TDT analysis showed no preferential transmission of allele 7 to ADHD probands. | Significant |
McCracken JT, 2000 | TDT of haplotype: P=0.04 for 120/-7; P=0.196 for 120/+7; P=0.297 for 240/-7; P=0.165 for 240/+7. Results in this study suggest that the 240-bp (long) allele of the 120-bp repeat polymorphism in the 5' untranslated region of DRD4 is preferentially transmitted from parents to their ADHD offspring. | Significant |
Sunohara GA, 2000 | The results of this study further support the possibility of a role of the dopamine D4 receptor locus in ADHD | Significant |
Barr CL, 2001(d) | allele-wise TDT P-value>0.059, the result was not significant for any of the haplotypes of the 5' polymorphisms; the overall allele-wise TDT X2 and genotype-wise TDT X2 for the haplotypes of the 5' polymorphisms were not significant. Allele-wise TDT X2=3.903, d.f.=1, P-value=0.048 for haplotype composed of 2 repeats of the 120 bp polymorphism, allele 2 (T) of the FspI polymorphism, allele 1 (C) of the AvaII polymorphism and the 7-repeat allele of exon III (2-2-1-7) showed significant evidence for biased transmission; The overall genotype-wise TDT X2 for the haplotypes of the 5' polymorphisms and the exon III polymorphism was significant (TDT X2=68.282, 43 d.f., P=0.009) but the overall allele-wise TDT X2 was not | Significant |
Barr CL, 2000 (b) | TDT of DRD4 haplotypes: smallest P=0.02; the current study of additional polymorphisms and haplotypes at the DRD4 locus further suggests that it is a susceptibility factor in ADHD. | Significant |
Hawi Z, 2000 (a) | no significant differences in the frequency of the DRD4 alleles transmitted or not transmitted to ADHD cases from their parents nor when comparing case allele frequencies to ethnically matched controls. | Non-significant |
Muglia P, 2000 | The results of this study suggest a role of the 7-repeat allele of DRD4 in adult subjects suffering from ADHD. | Significant |
Kotler M, 2000 | there was a significant excess of the long DRD4 repeat alleles in the HRR control group. | Significant |
Faraone SV, 1999 | The results suggest that there may be an association between ADHD and the 7-repeat allele of the dopamine D4 gene in this sample | Significant |
Comings DE, 1999 | 48bp repeat polymorphism is significantly associated with ADHD | Significant |
Tahir E, 2000 (b) | increased transmission of the DRD4 7-repeat allele was found | Significant |
Eisenberg J, 2000 | Current study failed to observe preferential transmission of the DRD4 exon III long 7 repeat allele (P<0.1). Nor was any preferential transmission observed when genotypes were compared (P>0.1) | Non-significant |
Swanson JM, 1998 | The HRR contingency statistic of allele 7 repeat was significant. This provides additional evidence that the DRD4 gene is associated with a refined phenotype of ADHD. | Significant |
Rowe DC, 1998 | Findings in this study were most positive for the questionnaire-based diagnosis of ADHD-inattentive type. | Significant |
Smalley SL, 1998 | In this study, they found evidence that the 7-repeat allele of DRD4 VNTR in exon 3 is transmitted to affected offspring more than non-7 repeat alleles suggesting that the 7-repeat allele is a susceptibility gene in ADHD. | Significant |
Castellanos FX, 1998 | There were no significant differences between cases and controls in the frequency of any allele and genotype | Non-significant |
Kirley A, 2004 | there was no association between the investigated variants and ADHD | Non-significant |
Bakker SC, 2005 | haplotype DRD4, TDT P-value=0.65; DRD4 did not contribute substantially to ADHD in the Dutch population | Non-significant |
Qian Q, 2004 | no evidence for association for either the entire sample or for DSM-IV subtypes of ADHD, but stratification by gender yielded intriguing results. Long repeat alleles were associated with ADHD in males but short repeats were associated with ADHD in females. | Significant |
Arcos-Burgos M, 2004 (b) | PDT smallest P=0.0467 for haplotype 240bp/7R, the haplotype analysis shows a significant association/linkage of the 7R-240 bp haplotype with ADHD. | Significant |
Kustanovich V, 2004 | The DRD4 gene 120-bp insertion/deletion promoter polymorphism displayed a significant bias in transmission of the insertion. The seven repeat allele of the DRD4 48-bp repeat polymorphism was not significantly associated with ADHD. | Significant |
Mill J, 2003 | haplotype (2-C-C-142-4) P-value=0.04, X2=4.073, 1 df, showed marginal evidence for biased transmission to ADHD probands; of which haplotype (2-C-C) P-value=0.03, X2=4.68, 1 df, was over-transmitted to affected ADHD probands | Significant |
Smith KM, 2003 | no polymorphism was significantly associated with ADHD | Non-significant |
Maher BS, 2002 | for DRD4, positive association was demostrated with ADHD in the meta-analysis and there was no support for hetergeneity between studies | Significant |
Kirley A, 2002 | No preferential transmission of alleles to ADHD children was observed | Non-significant |
Manor I, 2002 (a) | preferential transmission of the short allele of DRD4 exon 3 VNTR was observed | Significant |
Holmes J, 2002 | evidence of linkage and association between DRD4 and ADHD was found in this study | Significant |
Roman T, 2001 | an excess of the 7-repeat allele was observed when both ADHD probands and their parents were compared with an ethnically matched control sample, no main effects of DRD4 and ADHD by using dimensional Analyses | Significant |
Payton A, 2001 | there was no evidence of preferential transmission of any marker allele for the polymorphism examined in this study | Non-significant |
Todd RD, 2001(b) | combined haplotype of 5' 120bp RP and exon3 48bp RP, ETDT P-value>0.08 in DSM-IV subtype; haplotype (1-7) ETDT P-value=0.04, corrected P-value=0.25 in DSM-IV any ADHD; there was suggestive evidence for biased transmission | Significant |
Mill J, 2001 | there was evidence of association between 7 repeat allele of a 48 base-pair repeat in the dopamine D4 receptor gene in the case-control sample, but no evidence of linkage in the family-based UK sample | Significant |
Faraone SV, 2001 | both the case-control and family-based studies supported for the association between ADHD and DRD4 | Significant |
Kereszturi E, 2007 | haplotype frequency analysis: P-value=0.093 (df=9) under an unequal distribution; P-value=0.002 (OR=2.33) for 1-C-A-T haplotype. The 1-repeat form of the 120-bp dup in this gene was significantly higher in the ADHD group compared to controls. The 1-C-A-T haplotype was overrepresented in the cases. | Significant |
Brookes KJ, 2008(c) | DRD4 7-repeat allele is associated with ADHD | Significant |
Qian Q, 2007 | Logistic Regression Analysis: P-value=0.039, OR=2.805, 95%CI=1.056-7.452. Result show that the effects of the risk alleles of DRD4 found in the univariate analyses remained significant after partialing out the effects of the other putative risk alleles. | Significant |
Gornick MC, 2007 | The DRD4 7-repeat allele was significantly more frequent in ADHD cases than controls. | Significant |
Brookes K, 2006 | UNPHASED TDT P-value=0.055, global P-value=0.182, WHAP TDT P_sum P-value=0.132; OR=1.7, one or more SNPs with nominal P-value<0.05 located in this gene | Significant |
Cheuk DK, 2006(a) | 4/4 repeat genotype chi-square P-value=0.26, OR=1.52; 2/4 repeat genotype chi-square P-value=0.15, OR=0.55; the longer repeat genotypes chi-square P-value=0.01; P-value=0.013 in the male subgroup; P-value=0.005 in the inattentive subtype; a significant trend between the longer repeat alleles and ADHD | Significant |
Hawi Z, 2005 | one marker showed significant overtransmission of paternal alleles; paternal versus maternal transmissions, combined TDT P-value=0.0019, X2=9.6 (1df), OR=1.56; TDT P-value=0.0011, X2=10.6 when DRD4 was removed in sensitivity analysis | Significant |
Li D, 2006 | DRD4 4-repeat, 5-repeat, 7-repeat showed significant associations, there is a statistically significant association between ADHD and DRD4 | Significant |
Bhaduri N, 2006 (a) | haplotype 1-1-1 of the 5' flanking 120-bp duplication, exon 1 12-bp duplication, and exon 3 48-bp VNTR, haplotype frequencies P-value=0.0009, X2 (1df)=10.93 in cases, P-value=0.0091, X2 (1df)=6.8 in controls | Significant |
Carrasco X, 2006 | DRD4 7-repeat alleles Fisher¡¯s exact test P-value>0.25, DRD4 7-repeat heterozygosity and SLC6A3 10 allele homozygosity Fisher¡¯s exact test P-value=0.0096; OR=12.71, suggested evidence of gene-gene interaction effects on the prevalence of ADHD in the Chilean population | Significant |
Kim YS, 2005 | did not show preferential transmission of any allele or gene-gene interaction | Non-significant |
Todd RD, 2005 | no significant associations were found for DRD4 polymorphisms using DSM-IV ADHD subtypes | Non-significant |
Bobb AJ, 2005 | no polymorphism was associated with ADHD | Non-significant |
Brookes KJ, 2005 (a) | two-marker haplotype, TDT P-value=0.45; HHRR P-value=0.45; did not find either global or haplotype-specific evidence for association | Non-significant |
Lowe N, 2004 (a) | significant over transmission of SNP in DRD4 was observed. | Significant |
Leung PW, 2005 | chi-square analysis confirmed a significant increase in the frequency of the 2R allele of DRD4 in the Han Chinese ADHD probands compared to ethnically-matched controls from the five Han Chinese communities | Significant |
Literature-origin SNPs (count: 8)
rs_ID | Location | Functional Annotation | No. of Studies (significant/non-significant/trend) |
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rs936461 | Chr11:636496(Fwd) | upstream_gene_variant | 1(0/1/0) |
rs7124601 | Chr11:639273(Fwd) | downstream_gene_variant; intron_variant; nc_transcript_variant | 1(1/0/0) |
rs3758653 | Chr11:636399(Fwd) | upstream_gene_variant | 2(1/1/0) |
rs1800955 | Chr11:636784(Fwd) | upstream_gene_variant | 3(2/1/0) |
rs17758 | Chr11:644325(Fwd) | 3_prime_UTR_variant; NMD_transcript_variant; downstream_gene_variant; nc_transcript_variant; non_coding_exon_variant | 1(0/1/0) |
rs12720373 | Chr11:636688(Fwd) | upstream_gene_variant | 1(1/0/0) |
rs916457 | Chr11:637014(Fwd) | upstream_gene_variant | 1(1/0/0) |
rs916455 | Chr11:636929(Fwd) | upstream_gene_variant | 2(0/2/0) |
LD-proxies (count: 0)
Variant Name | Variant Type | Location in Gene | No. of Studies (significant/non-significant/trend) |
---|---|---|---|
DRD4_promoter_duplication_120bp | insertion/deletion | promoter | 13 (4/9/0) |
DRD4_exon3_VNTR | VNTR | exon 3 | 58 (33/25/0) |
DRD4_intron1_(G)n | microsatellite | intron 1 | 3 (0/3/0) |
DRD4_exon1_ins/del_12bp | insertion/deletion | exon 1 | 2 (0/2/0) |
DRD4_promoter_-615A/G | point mutation | promoter | 1 (0/1/0) |
DRD4_promoter_-616C/G | point mutation | promoter | 5 (1/4/0) |
DRD4_promoter_-376C/T | point mutation | promoter | 2 (0/2/0) |
DRD4_promoter_-521C/T | point mutation | promoter | 6 (0/6/0) |
GO terms by PBA (with statistical significance of FDR<0.05) (count: 0)
GO terms by database search (count: 43)
ID | Name | No. of Genes in ADHDgene | Brief Description |
---|---|---|---|
hsa04080 | Neuroactive ligand-receptor interaction | 93 |
Region: chr11:637293..640706 View in gBrowse
Copyright: Bioinformatics Lab, Institute of Psychology, Chinese Academy of Sciences Feedback
Last update: Feb 26, 2014