File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder

TitleDisease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder
Authors
Issue Date2011
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 2011, v. 20 n. 24, p. 4786-4796 How to Cite?
AbstractStudies of the major psychoses, schizophrenia (SZ) and bipolar disorder (BD), have traditionally focused on genetic and environmental risk factors, although more recent work has highlighted an additional role for epigenetic processes in mediating susceptibility. Since monozygotic (MZ) twins share a common DNA sequence, their study represents an ideal design for investigating the contribution of epigenetic factors to disease etiology. We performed a genome-wide analysis of DNA methylation on peripheral blood DNA samples obtained from a unique sample of MZ twin pairs discordant for major psychosis. Numerous loci demonstrated disease-associated DNA methylation differences between twins discordant for SZ and BD individually, and together as a combined major psychosis group. Pathway analysis of our top loci highlighted a significant enrichment of epigenetic changes in biological networks and pathways directly relevant to psychiatric disorder and neurodevelopment. The top psychosis-associated, differentially methylated region, significantly hypomethylated in affected twins, was located in the promoter of ST6GALNAC1 overlapping a previously reported rare genomic duplication observed in SZ. The mean DNA methylation difference at this locus was 6%, but there was considerable heterogeneity between families, with some twin pairs showing a 20% difference in methylation. We subsequently assessed this region in an independent sample of postmortem brain tissue from affected individuals and controls, finding marked hypomethylation (>25%) in a subset of psychosis patients. Overall, our data provide further evidence to support a role for DNA methylation differences in mediating phenotypic differences between MZ twins and in the etiology of both SZ and BD. © The Author 2011. Published by Oxford University Press. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/161251
ISSN
2015 Impact Factor: 5.985
2015 SCImago Journal Rankings: 4.288
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDempster, ELen_US
dc.contributor.authorPidsley, Ren_US
dc.contributor.authorSchalkwyk, LCen_US
dc.contributor.authorOwens, Sen_US
dc.contributor.authorGeorgiades, Aen_US
dc.contributor.authorKane, Fen_US
dc.contributor.authorKalidindi, Sen_US
dc.contributor.authorPicchioni, Men_US
dc.contributor.authorKravariti, Een_US
dc.contributor.authorToulopoulou, Ten_US
dc.contributor.authorMurray, RMen_US
dc.contributor.authorMill, Jen_US
dc.date.accessioned2012-08-23T06:11:25Z-
dc.date.available2012-08-23T06:11:25Z-
dc.date.issued2011en_US
dc.identifier.citationHuman Molecular Genetics, 2011, v. 20 n. 24, p. 4786-4796en_US
dc.identifier.issn0964-6906en_US
dc.identifier.urihttp://hdl.handle.net/10722/161251-
dc.description.abstractStudies of the major psychoses, schizophrenia (SZ) and bipolar disorder (BD), have traditionally focused on genetic and environmental risk factors, although more recent work has highlighted an additional role for epigenetic processes in mediating susceptibility. Since monozygotic (MZ) twins share a common DNA sequence, their study represents an ideal design for investigating the contribution of epigenetic factors to disease etiology. We performed a genome-wide analysis of DNA methylation on peripheral blood DNA samples obtained from a unique sample of MZ twin pairs discordant for major psychosis. Numerous loci demonstrated disease-associated DNA methylation differences between twins discordant for SZ and BD individually, and together as a combined major psychosis group. Pathway analysis of our top loci highlighted a significant enrichment of epigenetic changes in biological networks and pathways directly relevant to psychiatric disorder and neurodevelopment. The top psychosis-associated, differentially methylated region, significantly hypomethylated in affected twins, was located in the promoter of ST6GALNAC1 overlapping a previously reported rare genomic duplication observed in SZ. The mean DNA methylation difference at this locus was 6%, but there was considerable heterogeneity between families, with some twin pairs showing a 20% difference in methylation. We subsequently assessed this region in an independent sample of postmortem brain tissue from affected individuals and controls, finding marked hypomethylation (>25%) in a subset of psychosis patients. Overall, our data provide further evidence to support a role for DNA methylation differences in mediating phenotypic differences between MZ twins and in the etiology of both SZ and BD. © The Author 2011. Published by Oxford University Press. All rights reserved.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.subject.meshBipolar Disorder - Geneticsen_US
dc.subject.meshCpg Islands - Geneticsen_US
dc.subject.meshDna Methylation - Geneticsen_US
dc.subject.meshDemographyen_US
dc.subject.meshEpigenesis, Geneticen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Regulatory Networks - Geneticsen_US
dc.subject.meshGenetic Predisposition To Diseaseen_US
dc.subject.meshGenome, Human - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshReproducibility Of Resultsen_US
dc.subject.meshSchizophrenia - Geneticsen_US
dc.subject.meshTwins, Monozygotic - Geneticsen_US
dc.subject.meshYoung Adulten_US
dc.titleDisease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorderen_US
dc.typeArticleen_US
dc.identifier.emailToulopoulou, T:timothea@hku.hken_US
dc.identifier.authorityToulopoulou, T=rp01542en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1093/hmg/ddr416en_US
dc.identifier.pmid21908516-
dc.identifier.pmcidPMC3221539-
dc.identifier.scopuseid_2-s2.0-81855183787en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-81855183787&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume20en_US
dc.identifier.issue24en_US
dc.identifier.spage4786en_US
dc.identifier.epage4796en_US
dc.identifier.isiWOS:000297242100003-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridDempster, EL=8414816000en_US
dc.identifier.scopusauthoridPidsley, R=35218215500en_US
dc.identifier.scopusauthoridSchalkwyk, LC=7003409002en_US
dc.identifier.scopusauthoridOwens, S=36027261600en_US
dc.identifier.scopusauthoridGeorgiades, A=35233211400en_US
dc.identifier.scopusauthoridKane, F=24829114900en_US
dc.identifier.scopusauthoridKalidindi, S=24366595400en_US
dc.identifier.scopusauthoridPicchioni, M=6507443795en_US
dc.identifier.scopusauthoridKravariti, E=8855469000en_US
dc.identifier.scopusauthoridToulopoulou, T=8855468700en_US
dc.identifier.scopusauthoridMurray, RM=35406239400en_US
dc.identifier.scopusauthoridMill, J=7006450209en_US
dc.identifier.citeulike9756383-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats