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Article: Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD)

TitleMeta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD)
Authors
Issue Date2006
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 2006, v. 15 n. 14, p. 2276-2284 How to Cite?
AbstractMolecular genetic investigations of attention deficit hyperactivity disorder (ADHD) have found associations with a variable number of tandem repeat (VNTR) situated in the 3′-untranslated region of dopamine transporter gene (DAT1), a VNTR in exon 3 of dopamine receptor 4 gene (DRD4) and a microsatellite polymorphism located at 18.5 kb from the 5′ end of dopamine receptor 5 gene (DRD5). A number of independent studies have attempted to replicate these findings but the results have been mixed, possibly reflecting inadequate statistical power and the use of different populations and methodologies. In an attempt to clarify this inconsistency, we have combined all the published studies of European and Asian populations up to October 2005 in a meta-analysis to give a comprehensive picture of the role of the three dopamine-related genes using multiple research methods and models. The DRD4 7-repeat (OR = 1.34, 95% CI 1.23-1.45, P = 2 × 10-12) and 5-repeat (OR = 1.68, 95% CI 1.17-2.41, P = 0.005) alleles as well as the DRD5 148-bp allele (OR=1.34, 95% CI 1.21-1.49, P = 8 × 10-8) confer increased risk of ADHD, whereas the DRD4 4-repeat (OR = 0.90, 95% CI 0.84-0.97, P = 0.004) and DRD5 136-bp (OR = 0.57, 95% CI 0.34-0.96, P = 0.022) alleles have protective effects. In contrast, we found no compelling evidence for association with the 480-bp allele of DAT (OR=1.04, 95% CI 0.98-1.11, P = 0.20). No significant publication bias was detected in current studies. In conclusion, there is a statistically significant association between ADHD and dopamine system genes, especially DRD4 and DRD5. These findings strongly implicate the involvement of brain dopamine systems in the pathogenesis of ADHD. © 2006 Oxford University Press.
Persistent Identifierhttp://hdl.handle.net/10722/175952
ISSN
2015 Impact Factor: 5.985
2015 SCImago Journal Rankings: 4.288
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, DWen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorOwen, MJen_US
dc.contributor.authorHe, Len_US
dc.date.accessioned2012-11-26T09:02:50Z-
dc.date.available2012-11-26T09:02:50Z-
dc.date.issued2006en_US
dc.identifier.citationHuman Molecular Genetics, 2006, v. 15 n. 14, p. 2276-2284en_US
dc.identifier.issn0964-6906en_US
dc.identifier.urihttp://hdl.handle.net/10722/175952-
dc.description.abstractMolecular genetic investigations of attention deficit hyperactivity disorder (ADHD) have found associations with a variable number of tandem repeat (VNTR) situated in the 3′-untranslated region of dopamine transporter gene (DAT1), a VNTR in exon 3 of dopamine receptor 4 gene (DRD4) and a microsatellite polymorphism located at 18.5 kb from the 5′ end of dopamine receptor 5 gene (DRD5). A number of independent studies have attempted to replicate these findings but the results have been mixed, possibly reflecting inadequate statistical power and the use of different populations and methodologies. In an attempt to clarify this inconsistency, we have combined all the published studies of European and Asian populations up to October 2005 in a meta-analysis to give a comprehensive picture of the role of the three dopamine-related genes using multiple research methods and models. The DRD4 7-repeat (OR = 1.34, 95% CI 1.23-1.45, P = 2 × 10-12) and 5-repeat (OR = 1.68, 95% CI 1.17-2.41, P = 0.005) alleles as well as the DRD5 148-bp allele (OR=1.34, 95% CI 1.21-1.49, P = 8 × 10-8) confer increased risk of ADHD, whereas the DRD4 4-repeat (OR = 0.90, 95% CI 0.84-0.97, P = 0.004) and DRD5 136-bp (OR = 0.57, 95% CI 0.34-0.96, P = 0.022) alleles have protective effects. In contrast, we found no compelling evidence for association with the 480-bp allele of DAT (OR=1.04, 95% CI 0.98-1.11, P = 0.20). No significant publication bias was detected in current studies. In conclusion, there is a statistically significant association between ADHD and dopamine system genes, especially DRD4 and DRD5. These findings strongly implicate the involvement of brain dopamine systems in the pathogenesis of ADHD. © 2006 Oxford University Press.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/en_US
dc.relation.ispartofHuman Molecular Geneticsen_US
dc.rightsHuman Molecular Genetics. Copyright © Oxford University Press.-
dc.subject.mesh3' Untranslated Regionsen_US
dc.subject.meshAllelesen_US
dc.subject.meshAttention Deficit Disorder With Hyperactivity - Geneticsen_US
dc.subject.meshDopamine - Geneticsen_US
dc.subject.meshDopamine Plasma Membrane Transport Proteins - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshMinisatellite Repeatsen_US
dc.subject.meshReceptors, Dopamine D4 - Geneticsen_US
dc.subject.meshReceptors, Dopamine D5 - Geneticsen_US
dc.subject.meshRisk Factorsen_US
dc.subject.meshSensitivity And Specificityen_US
dc.titleMeta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD)en_US
dc.typeArticleen_US
dc.identifier.emailSham, PC: pcsham@hku.hken_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1093/hmg/ddl152en_US
dc.identifier.pmid16774975-
dc.identifier.scopuseid_2-s2.0-33745700886en_US
dc.identifier.hkuros134321-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33745700886&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume15en_US
dc.identifier.issue14en_US
dc.identifier.spage2276en_US
dc.identifier.epage2284en_US
dc.identifier.isiWOS:000238762800010-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.f10001047380-
dc.identifier.scopusauthoridLi, D=8236324800en_US
dc.identifier.scopusauthoridSham, PC=34573429300en_US
dc.identifier.scopusauthoridOwen, MJ=36044041500en_US
dc.identifier.scopusauthoridHe, L=36080215400en_US
dc.identifier.citeulike742139-
dc.customcontrol.immutablesml 140918-

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