title: CNVs conferring risk of autism or schizophrenia affect cognition in controls.
abstract: In 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.
authors.affiliation: 1] deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland [2].
authors.forename: Hreinn
authors.initials: H
authors.lastname: Stefansson
authors.affiliation: 1] Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany [2].
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg
authors.affiliation: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland.
authors.forename: Stacy
authors.initials: S
authors.lastname: Steinberg
authors.affiliation: Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavík, Iceland.
authors.forename: Brynja
authors.initials: B
authors.lastname: Magnusdottir
authors.affiliation: Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Morgen
authors.affiliation: 1] deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland [2] Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavík, Iceland.
authors.forename: Sunna
authors.initials: S
authors.lastname: Arnarsdottir
authors.affiliation: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland.
authors.forename: Gyda
authors.initials: G
authors.lastname: Bjornsdottir
authors.affiliation: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland.
authors.forename: G Bragi
authors.initials: GB
authors.lastname: Walters
authors.affiliation: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland.
authors.forename: Gudrun A
authors.initials: GA
authors.lastname: Jonsdottir
authors.affiliation: Institute of Psychiatry, King's College, 16 De Crespigny Park, London SE5 8AF, UK.
authors.forename: Orla M
authors.initials: OM
authors.lastname: Doyle
authors.affiliation: Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Tost
authors.affiliation: Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Grimm
authors.affiliation: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland.
authors.forename: Solveig
authors.initials: S
authors.lastname: Kristjansdottir
authors.affiliation: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland.
authors.forename: Heimir
authors.initials: H
authors.lastname: Snorrason
authors.affiliation: Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavík, Iceland.
authors.forename: Solveig R
authors.initials: SR
authors.lastname: Davidsdottir
authors.affiliation: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland.
authors.forename: Larus J
authors.initials: LJ
authors.lastname: Gudmundsson
authors.affiliation: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland.
authors.forename: Gudbjorn F
authors.initials: GF
authors.lastname: Jonsson
authors.affiliation: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland.
authors.forename: Berglind
authors.initials: B
authors.lastname: Stefansdottir
authors.affiliation: Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavík, Iceland.
authors.forename: Isafold
authors.initials: I
authors.lastname: Helgadottir
authors.affiliation: 1] Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavík, Iceland [2] University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland.
authors.forename: Magnus
authors.initials: M
authors.lastname: Haraldsson
authors.affiliation: Röntgen Domus, Egilsgötu 3, IS-101 Reykjavík, Iceland.
authors.forename: Birna
authors.initials: B
authors.lastname: Jonsdottir
authors.affiliation: Mental Health Centre Sct. Hans, Copenhagen University Hospital, Research Institute of Biological Psychiatry, Boserupvej 2, DK-4000 Roskilde, Denmark.
authors.forename: Johan H
authors.initials: JH
authors.lastname: Thygesen
authors.affiliation: Tailored Therapeutics, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center DC 1940, Indianapolis, Indiana 46285, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Schwarz
authors.affiliation: H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Didriksen
authors.affiliation: H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
authors.forename: Tine B
authors.initials: TB
authors.lastname: Stensbøl
authors.affiliation: Institute of Psychiatry, King's College, 16 De Crespigny Park, London SE5 8AF, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Brammer
authors.affiliation: Institute of Psychiatry, King's College, 16 De Crespigny Park, London SE5 8AF, UK.
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.affiliation: University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland.
authors.forename: Jonas G
authors.initials: JG
authors.lastname: Halldorsson
authors.affiliation: The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kópavogur, Iceland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hreidarsson
authors.affiliation: 1] University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland [2] The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kópavogur, Iceland.
authors.forename: Evald
authors.initials: E
authors.lastname: Saemundsen
authors.affiliation: 1] Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavík, Iceland [2] University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland.
authors.forename: Engilbert
authors.initials: E
authors.lastname: Sigurdsson
authors.affiliation: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001321:Autistic Disorder / Q000235:genetics*; D001921:Brain / Q000002:abnormalities / Q000033:anatomy & histology / Q000378:metabolism; D016022:Case-Control Studies; D002872:Chromosome Deletion; D002877:Chromosomes, Human / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D056915:DNA Copy Number Variations / Q000235:genetics*; D004410:Dyslexia / Q000235:genetics; D005260:Female; D005298:Fertility / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007055:Iceland; D007859:Learning Disabilities / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult