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dc.contributor.authorStefansson, Hreinn
dc.contributor.authorMeyer-Lindenberg, Andreas
dc.contributor.authorSteinberg, Stacy
dc.contributor.authorMagnusdottir, Brynja
dc.contributor.authorMorgen, Katrin
dc.contributor.authorArnarsdottir, Sunna
dc.contributor.authorBjornsdottir, Gyda
dc.contributor.authorWalters, G Bragi
dc.contributor.authorJonsdottir, Gudrun A
dc.contributor.authorDoyle, Orla M
dc.contributor.authorTost, Heike
dc.contributor.authorGrimm, Oliver
dc.contributor.authorKristjansdottir, Solveig
dc.contributor.authorSnorrason, Heimir
dc.contributor.authorDavidsdottir, Solveig R
dc.contributor.authorGudmundsson, Larus J
dc.contributor.authorJonsson, Gudbjorn F
dc.contributor.authorStefansdottir, Berglind
dc.contributor.authorHelgadottir, Isafold
dc.contributor.authorHaraldsson, Magnus
dc.contributor.authorJonsdottir, Birna
dc.contributor.authorThygesen, Johan H
dc.contributor.authorSchwarz, Adam J
dc.contributor.authorDidriksen, Michael
dc.contributor.authorStensbøl, Tine B
dc.contributor.authorBrammer, Michael
dc.contributor.authorKapur, Shitij
dc.contributor.authorHalldorsson, Jonas G
dc.contributor.authorHreidarsson, Stefan
dc.contributor.authorSaemundsen, Evald
dc.contributor.authorSigurdsson, Engilbert
dc.contributor.authorStefansson, Kari
dc.date.accessioned2014-01-21T09:28:42Z
dc.date.available2014-01-21T09:28:42Z
dc.date.issued2014
dc.identifier.citationNature 2014, 505 (7483):361-6en
dc.identifier.issn1476-4687
dc.identifier.pmid24352232
dc.identifier.doi10.1038/nature12818
dc.identifier.urihttp://hdl.handle.net/2336/311615
dc.descriptionTo access publisher's full text version of this article click on the hyperlink at the bottom of the pageen
dc.description.abstractIn a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.
dc.description.sponsorshipinfo:eu-repo/grantAgreement/EC/FP/286213/EU//OpenAIREplusen
dc.description.sponsorshipinfo:eu-repo/grantAgreement/EC/FP7/286213en
dc.language.isoenen
dc.publisherNPGen
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/286213en
dc.relation.urlhttp://dx.doi.org/10.1038/nature12818en
dc.relation.urlhttp://www.nature.com/nature/journal/v505/n7483/pdf/nature12818.pdf
dc.rightsopenAccessen
dc.subjectGeðklofi
dc.subjectEinhverfa
dc.subjectArfgengi
dc.subject.meshAdolescent
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAutistic Disorder/genetics*
dc.subject.meshBrain/abnormalities
dc.subject.meshBrain/anatomy & histology
dc.subject.meshBrain/metabolism
dc.subject.meshCase-Control Studies
dc.subject.meshChromosome Deletion
dc.subject.meshChromosomes, Human/genetics
dc.subject.meshChromosomes, Human, Pair 15/genetics
dc.subject.meshCognition/physiology*
dc.subject.meshDNA Copy Number Variations/genetics*
dc.subject.meshDyslexia/genetics
dc.subject.meshFemale
dc.subject.meshFertility/genetics
dc.subject.meshGenetic Predisposition to Disease*
dc.subject.meshHeterozygote
dc.subject.meshHumans
dc.subject.meshIceland
dc.subject.meshLearning Disorders/genetics
dc.subject.meshMagnetic Resonance Imaging
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshNeuropsychological Tests
dc.subject.meshPhenotype
dc.subject.meshSchizophrenia/genetics*
dc.subject.meshYoung Adult
dc.titleCNVs conferring risk of autism or schizophrenia affect cognition in controls.en
dc.typearticleen
dc.contributor.departmentdeCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland, Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany, Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavík, Iceland, Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany, Institute of Psychiatry, King's College, 16 De Crespigny Park, London SE5 8AF, UK, University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland, Röntgen Domus, Egilsgötu 3, IS-101 Reykjavík, Iceland, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Research Institute of Biological Psychiatry, Boserupvej 2, DK-4000 Roskilde, Denmark, Tailored Therapeutics, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center DC 1940, Indianapolis, Indiana 46285, USA, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark, The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kópavogur, Icelanden
dc.identifier.journalNatureen
dc.rights.accessOpen Accessen
refterms.dateFOA2018-09-12T13:10:47Z
html.description.abstractIn a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.


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