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Article: Substantial genetic overlap between neurocognition and schizophrenia: Genetic modeling in twin samples

TitleSubstantial genetic overlap between neurocognition and schizophrenia: Genetic modeling in twin samples
Authors
Issue Date2007
PublisherAmerican Medical Association. The Journal's web site is located at http://www.archgenpsychiatry.com
Citation
Archives Of General Psychiatry, 2007, v. 64 n. 12, p. 1348-1355 How to Cite?
AbstractContext: The use of endophenotypes, biological traits that increase the liability to a disorder, represents one strategy to facilitate the detection of susceptibility genes for complex behavioral disorders such as schizophrenia. Establishing that a candidate trait is both heritable and linked genetically to schizophrenia is integral to its validity as an endophenotypic marker. Neurocognitive deficits are among the most promising indicators of increased risk for schizophrenia; however, it is not clear to what extent these deficits are genetically linked to the disorder. Objectives: To quantify the genetic and environmental contributions to the variability of selected neurocognitive measures and to estimate the genetic relationship between these and schizophrenia. Design: Genetic model fitting to monozygotic and dizygotic twin data. Setting: United Kingdom psychiatric research institute. Participants: Two hundred sixty-seven monozygotic and dizygotic twins concordant and discordant for schizophrenia, and healthy monozygotic and dizygotic control twin pairs. Main Outcome Measures: The heritabilities of intelligence, working memory, processing speed, perceptual organization, and verbal comprehension were estimated, and the genetic relationship between each of these and schizophrenia was quantified. Results: Genetic influences contributed substantially to all of the cognitive domains, but intelligence and working memory were the most heritable. A significant correlation was found between intelligence and schizophrenia (r=-0.61; 95% confidence interval, -0.71 to -0.48), with shared genetic variance accounting for 92% of the covariance between the two. Genetic influences also explained most of the covariance between working memory and schizophrenia. Significant but lesser portions of covariance between the other cognitive domains and schizophrenia were also found to be genetically shared. Environmental effects, although separately linked to neurocognition and schizophrenia, did not generally contribute to their covariance. Conclusion: Genomewide searches using factorial designs stratifying for levels of intelligence and working memory will assist in the search for finding quantitative trait loci for schizophrenia. ©2007 American Medical Association. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/81459
ISSN
2014 Impact Factor: 14.48
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorToulopoulou, Ten_HK
dc.contributor.authorPicchioni, Men_HK
dc.contributor.authorRijsdijk, Fen_HK
dc.contributor.authorHuaHall, Men_HK
dc.contributor.authorEttinger, Uen_HK
dc.contributor.authorSham, Pen_HK
dc.contributor.authorMurray, Ren_HK
dc.date.accessioned2010-09-06T08:18:01Z-
dc.date.available2010-09-06T08:18:01Z-
dc.date.issued2007en_HK
dc.identifier.citationArchives Of General Psychiatry, 2007, v. 64 n. 12, p. 1348-1355en_HK
dc.identifier.issn0003-990Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/81459-
dc.description.abstractContext: The use of endophenotypes, biological traits that increase the liability to a disorder, represents one strategy to facilitate the detection of susceptibility genes for complex behavioral disorders such as schizophrenia. Establishing that a candidate trait is both heritable and linked genetically to schizophrenia is integral to its validity as an endophenotypic marker. Neurocognitive deficits are among the most promising indicators of increased risk for schizophrenia; however, it is not clear to what extent these deficits are genetically linked to the disorder. Objectives: To quantify the genetic and environmental contributions to the variability of selected neurocognitive measures and to estimate the genetic relationship between these and schizophrenia. Design: Genetic model fitting to monozygotic and dizygotic twin data. Setting: United Kingdom psychiatric research institute. Participants: Two hundred sixty-seven monozygotic and dizygotic twins concordant and discordant for schizophrenia, and healthy monozygotic and dizygotic control twin pairs. Main Outcome Measures: The heritabilities of intelligence, working memory, processing speed, perceptual organization, and verbal comprehension were estimated, and the genetic relationship between each of these and schizophrenia was quantified. Results: Genetic influences contributed substantially to all of the cognitive domains, but intelligence and working memory were the most heritable. A significant correlation was found between intelligence and schizophrenia (r=-0.61; 95% confidence interval, -0.71 to -0.48), with shared genetic variance accounting for 92% of the covariance between the two. Genetic influences also explained most of the covariance between working memory and schizophrenia. Significant but lesser portions of covariance between the other cognitive domains and schizophrenia were also found to be genetically shared. Environmental effects, although separately linked to neurocognition and schizophrenia, did not generally contribute to their covariance. Conclusion: Genomewide searches using factorial designs stratifying for levels of intelligence and working memory will assist in the search for finding quantitative trait loci for schizophrenia. ©2007 American Medical Association. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherAmerican Medical Association. The Journal's web site is located at http://www.archgenpsychiatry.comen_HK
dc.relation.ispartofArchives of General Psychiatryen_HK
dc.titleSubstantial genetic overlap between neurocognition and schizophrenia: Genetic modeling in twin samplesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0003-990X&volume=64&spage=1348&epage=1355&date=2007&atitle=Substantial+genetic+overlap+between+neurocognition+and+schizophrenia+-+Genetic+modelling+in+twin+samplesen_HK
dc.identifier.emailToulopoulou, T: timothea@hku.hken_HK
dc.identifier.emailSham, P: pcsham@hku.hken_HK
dc.identifier.authorityToulopoulou, T=rp01542en_HK
dc.identifier.authoritySham, P=rp00459en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1001/archpsyc.64.12.1348en_HK
dc.identifier.pmid18056542-
dc.identifier.scopuseid_2-s2.0-36849056624en_HK
dc.identifier.hkuros151606en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-36849056624&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume64en_HK
dc.identifier.issue12en_HK
dc.identifier.spage1348en_HK
dc.identifier.epage1355en_HK
dc.identifier.eissn2168-6238-
dc.identifier.isiWOS:000251374500002-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10001128819-
dc.identifier.scopusauthoridToulopoulou, T=8855468700en_HK
dc.identifier.scopusauthoridPicchioni, M=6507443795en_HK
dc.identifier.scopusauthoridRijsdijk, F=6701830835en_HK
dc.identifier.scopusauthoridHuaHall, M=23034969400en_HK
dc.identifier.scopusauthoridEttinger, U=6602766172en_HK
dc.identifier.scopusauthoridSham, P=34573429300en_HK
dc.identifier.scopusauthoridMurray, R=35406239400en_HK

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