2.50
Hdl Handle:
http://hdl.handle.net/2336/42220
Title:
Large recurrent microdeletions associated with schizophrenia
Authors:
Stefansson, Hreinn; Rujescu, Dan; Cichon, Sven; Pietiläinen, Olli P H; Ingason, Andres; Steinberg, Stacy; Fossdal, Ragnheidur; Sigurdsson, Engilbert; Sigmundsson, Thordur; Buizer-Voskamp, Jacobine E; Hansen, Thomas; Jakobsen, Klaus D; Muglia, Pierandrea; Francks, Clyde; Matthews, Paul M; Gylfason, Arnaldur; Halldorsson, Bjarni V; Gudbjartsson, Daniel; Thorgeirsson, Thorgeir E; Sigurdsson, Asgeir; Jonasdottir, Adalbjorg; Jonasdottir, Aslaug; Bjornsson, Asgeir; Mattiasdottir, Sigurborg; Blondal, Thorarinn; Haraldsson, Magnus; Magnusdottir, Brynja B; Giegling, Ina; Möller, Hans-Jürgen; Hartmann, Annette; Shianna, Kevin V; Ge, Dongliang; Need, Anna C; Crombie, Caroline; Fraser, Gillian; Walker, Nicholas; Lonnqvist, Jouko; Suvisaari, Jaana; Tuulio-Henriksson, Annamarie; Paunio, Tiina; Toulopoulou, Timi; Bramon, Elvira; Di Forti, Marta; Murray, Robin; Ruggeri, Mirella; Vassos, Evangelos; Tosato, Sarah; Walshe, Muriel; Li, Tao; Vasilescu, Catalina; Mühleisen, Thomas W; Wang, August G; Ullum, Henrik; Djurovic, Srdjan; Melle, Ingrid; Olesen, Jes; Kiemeney, Lambertus A; Franke, Barbara; Sabatti, Chiara; Freimer, Nelson B; Gulcher, Jeffrey R; Thorsteinsdottir, Unnur; Kong, Augustine; Andreassen, Ole A; Ophoff, Roel A; Georgi, Alexander; Rietschel, Marcella; Werge, Thomas; Petursson, Hannes; Goldstein, David B; Nöthen, Markus M; Peltonen, Leena; Collier, David A; St Clair, David; Stefansson, Kari
Citation:
Large recurrent microdeletions associated with schizophrenia. 2008, 455 (7210):232-6 Nature
Issue Date:
11-Sep-2008
Abstract:
Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1038/nature07229

Full metadata record

DC FieldValue Language
dc.contributor.authorStefansson, Hreinn-
dc.contributor.authorRujescu, Dan-
dc.contributor.authorCichon, Sven-
dc.contributor.authorPietiläinen, Olli P H-
dc.contributor.authorIngason, Andres-
dc.contributor.authorSteinberg, Stacy-
dc.contributor.authorFossdal, Ragnheidur-
dc.contributor.authorSigurdsson, Engilbert-
dc.contributor.authorSigmundsson, Thordur-
dc.contributor.authorBuizer-Voskamp, Jacobine E-
dc.contributor.authorHansen, Thomas-
dc.contributor.authorJakobsen, Klaus D-
dc.contributor.authorMuglia, Pierandrea-
dc.contributor.authorFrancks, Clyde-
dc.contributor.authorMatthews, Paul M-
dc.contributor.authorGylfason, Arnaldur-
dc.contributor.authorHalldorsson, Bjarni V-
dc.contributor.authorGudbjartsson, Daniel-
dc.contributor.authorThorgeirsson, Thorgeir E-
dc.contributor.authorSigurdsson, Asgeir-
dc.contributor.authorJonasdottir, Adalbjorg-
dc.contributor.authorJonasdottir, Aslaug-
dc.contributor.authorBjornsson, Asgeir-
dc.contributor.authorMattiasdottir, Sigurborg-
dc.contributor.authorBlondal, Thorarinn-
dc.contributor.authorHaraldsson, Magnus-
dc.contributor.authorMagnusdottir, Brynja B-
dc.contributor.authorGiegling, Ina-
dc.contributor.authorMöller, Hans-Jürgen-
dc.contributor.authorHartmann, Annette-
dc.contributor.authorShianna, Kevin V-
dc.contributor.authorGe, Dongliang-
dc.contributor.authorNeed, Anna C-
dc.contributor.authorCrombie, Caroline-
dc.contributor.authorFraser, Gillian-
dc.contributor.authorWalker, Nicholas-
dc.contributor.authorLonnqvist, Jouko-
dc.contributor.authorSuvisaari, Jaana-
dc.contributor.authorTuulio-Henriksson, Annamarie-
dc.contributor.authorPaunio, Tiina-
dc.contributor.authorToulopoulou, Timi-
dc.contributor.authorBramon, Elvira-
dc.contributor.authorDi Forti, Marta-
dc.contributor.authorMurray, Robin-
dc.contributor.authorRuggeri, Mirella-
dc.contributor.authorVassos, Evangelos-
dc.contributor.authorTosato, Sarah-
dc.contributor.authorWalshe, Muriel-
dc.contributor.authorLi, Tao-
dc.contributor.authorVasilescu, Catalina-
dc.contributor.authorMühleisen, Thomas W-
dc.contributor.authorWang, August G-
dc.contributor.authorUllum, Henrik-
dc.contributor.authorDjurovic, Srdjan-
dc.contributor.authorMelle, Ingrid-
dc.contributor.authorOlesen, Jes-
dc.contributor.authorKiemeney, Lambertus A-
dc.contributor.authorFranke, Barbara-
dc.contributor.authorSabatti, Chiara-
dc.contributor.authorFreimer, Nelson B-
dc.contributor.authorGulcher, Jeffrey R-
dc.contributor.authorThorsteinsdottir, Unnur-
dc.contributor.authorKong, Augustine-
dc.contributor.authorAndreassen, Ole A-
dc.contributor.authorOphoff, Roel A-
dc.contributor.authorGeorgi, Alexander-
dc.contributor.authorRietschel, Marcella-
dc.contributor.authorWerge, Thomas-
dc.contributor.authorPetursson, Hannes-
dc.contributor.authorGoldstein, David B-
dc.contributor.authorNöthen, Markus M-
dc.contributor.authorPeltonen, Leena-
dc.contributor.authorCollier, David A-
dc.contributor.authorSt Clair, David-
dc.contributor.authorStefansson, Kari-
dc.date.accessioned2008-12-11T11:42:00Z-
dc.date.available2008-12-11T11:42:00Z-
dc.date.issued2008-09-11-
dc.date.submitted2008-12-11-
dc.identifier.citationLarge recurrent microdeletions associated with schizophrenia. 2008, 455 (7210):232-6 Natureen
dc.identifier.issn0028-0836-
dc.identifier.pmid18668039-
dc.identifier.doi10.1038/nature07229-
dc.identifier.urihttp://hdl.handle.net/2336/42220-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractReduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urlhttp://dx.doi.org/10.1038/nature07229en
dc.subject.meshChinaen
dc.subject.meshChromosomes, Human, Pair 1en
dc.subject.meshChromosomes, Human, Pair 15en
dc.subject.meshEuropeen
dc.subject.meshGene Dosageen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGenome, Humanen
dc.subject.meshGenotypeen
dc.subject.meshHumansen
dc.subject.meshLoss of Heterozygosityen
dc.subject.meshModels, Geneticen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshPsychotic Disordersen
dc.subject.meshSchizophreniaen
dc.subject.meshSequence Deletionen
dc.titleLarge recurrent microdeletions associated with schizophreniaen
dc.typeArticleen
dc.identifier.eissn1476-4687-
dc.contributor.departmentCNS Division, deCODE genetics, Sturlugata 8, IS-101 Reykjavík, Iceland.en
dc.identifier.journalNatureen

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