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Article: Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: A systematic review and meta-analysis

TitlePopulation-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: A systematic review and meta-analysis
Authors
Issue Date2005
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/mp
Citation
Molecular Psychiatry, 2005, v. 10 n. 8, p. 771-781 How to Cite?
AbstractThe serotonin transporter (5-HTT) is a candidate gene for bipolar disorder (BPD). It has been investigated for association with the illness in a series of studies, but overall results have been inconsistent and its role in the disorder remains controversial. Systematic reviews using meta-analytical techniques are a useful method for objectively and reproducibly assessing individual studies and generating combined results. We performed two meta-analyses of published studies-both population-based and family-based studies-investigating the association between BPO and the 5-HTT gene-linked polymorphic region (5-HTTLPR) and the intron 2 variable numbers of tandem repeats (VNTR) polymorphisms. The literature was searched using Medline and Embase to identify studies for inclusion. We statistically joined population-based and family-based studies into a single meta-analysis. For both polymorphisms, our review revealed significant pooled odds ratios (ORs): 1.12 (95% CI 1.03-1.21) for the 5-HTTLPR and 1.12 (95% CI 1.02-1.22) for the intron 2 VNTR. Meta-regression showed that neither the study type (population-based vs family-based; P = 0.41 for the 5-HTTLPR and P = 0.91 for the intron 2 VNTR) nor the sample ethnicity (Caucasian vs non-Caucasian; P = 0.35 for the 5-HTTLPR and P = 0.66 for the intron 2 VNTR) significantly contributed to the heterogeneity of the meta-analyses. The observed ORs could be regarded simply as a very small but detectable effect of the 5-HTT, which has an additive effect when combined with other susceptibility loci. Alternative hypotheses on this finding were also discussed: a stronger effect of the haplotypes involving the two polymorphisms or other SNP markers; a more direct effect of these polymorphisms on specific phenotypes of BPD; and the presence of gene-environment interaction as a mediator of the genetic effects of 5-HTT. © 2005 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/175938
ISSN
2015 Impact Factor: 13.314
2015 SCImago Journal Rankings: 6.790
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCho, HJen_US
dc.contributor.authorMeiraLima, Ien_US
dc.contributor.authorCordeiro, Qen_US
dc.contributor.authorMichelon, Len_US
dc.contributor.authorSham, Pen_US
dc.contributor.authorVallada, Hen_US
dc.contributor.authorCollier, DAen_US
dc.date.accessioned2012-11-26T09:02:40Z-
dc.date.available2012-11-26T09:02:40Z-
dc.date.issued2005en_US
dc.identifier.citationMolecular Psychiatry, 2005, v. 10 n. 8, p. 771-781en_US
dc.identifier.issn1359-4184en_US
dc.identifier.urihttp://hdl.handle.net/10722/175938-
dc.description.abstractThe serotonin transporter (5-HTT) is a candidate gene for bipolar disorder (BPD). It has been investigated for association with the illness in a series of studies, but overall results have been inconsistent and its role in the disorder remains controversial. Systematic reviews using meta-analytical techniques are a useful method for objectively and reproducibly assessing individual studies and generating combined results. We performed two meta-analyses of published studies-both population-based and family-based studies-investigating the association between BPO and the 5-HTT gene-linked polymorphic region (5-HTTLPR) and the intron 2 variable numbers of tandem repeats (VNTR) polymorphisms. The literature was searched using Medline and Embase to identify studies for inclusion. We statistically joined population-based and family-based studies into a single meta-analysis. For both polymorphisms, our review revealed significant pooled odds ratios (ORs): 1.12 (95% CI 1.03-1.21) for the 5-HTTLPR and 1.12 (95% CI 1.02-1.22) for the intron 2 VNTR. Meta-regression showed that neither the study type (population-based vs family-based; P = 0.41 for the 5-HTTLPR and P = 0.91 for the intron 2 VNTR) nor the sample ethnicity (Caucasian vs non-Caucasian; P = 0.35 for the 5-HTTLPR and P = 0.66 for the intron 2 VNTR) significantly contributed to the heterogeneity of the meta-analyses. The observed ORs could be regarded simply as a very small but detectable effect of the 5-HTT, which has an additive effect when combined with other susceptibility loci. Alternative hypotheses on this finding were also discussed: a stronger effect of the haplotypes involving the two polymorphisms or other SNP markers; a more direct effect of these polymorphisms on specific phenotypes of BPD; and the presence of gene-environment interaction as a mediator of the genetic effects of 5-HTT. © 2005 Nature Publishing Group All rights reserved.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/mpen_US
dc.relation.ispartofMolecular Psychiatryen_US
dc.subject.meshBipolar Disorder - Etiology - Geneticsen_US
dc.subject.meshEnvironmenten_US
dc.subject.meshFamilyen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMembrane Glycoproteins - Geneticsen_US
dc.subject.meshMembrane Transport Proteins - Geneticsen_US
dc.subject.meshNerve Tissue Proteins - Geneticsen_US
dc.subject.meshPolymorphism, Geneticen_US
dc.subject.meshSerotonin Plasma Membrane Transport Proteinsen_US
dc.titlePopulation-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: A systematic review and meta-analysisen_US
dc.typeArticleen_US
dc.identifier.emailSham, P: pcsham@hku.hken_US
dc.identifier.authoritySham, P=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.mp.4001663en_US
dc.identifier.pmid15824745-
dc.identifier.scopuseid_2-s2.0-23744490895en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-23744490895&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume10en_US
dc.identifier.issue8en_US
dc.identifier.spage771en_US
dc.identifier.epage781en_US
dc.identifier.isiWOS:000230827800009-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridCho, HJ=8531834100en_US
dc.identifier.scopusauthoridMeiraLima, I=6602293581en_US
dc.identifier.scopusauthoridCordeiro, Q=6602193357en_US
dc.identifier.scopusauthoridMichelon, L=6508271838en_US
dc.identifier.scopusauthoridSham, P=34573429300en_US
dc.identifier.scopusauthoridVallada, H=7003742958en_US
dc.identifier.scopusauthoridCollier, DA=26642980600en_US
dc.identifier.citeulike159194-

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