CNVs conferring risk of autism or schizophrenia affect cognition in controls

Hreinn Stefansson, Andreas Meyer-Lindenberg (), Stacy Steinberg, Brynja Magnusdottir, Katrin Morgen, Sunna Arnarsdottir, Gyda Bjornsdottir, G. Bragi Walters, Gudrun A. Jonsdottir, Orla M. Doyle, Heike Tost, Oliver Grimm, Solveig Kristjansdottir, Heimir Snorrason, Solveig R. Davidsdottir, Larus J. Gudmundsson, Gudbjorn F. Jonsson, Berglind Stefansdottir, Isafold Helgadottir, Magnus Haraldsson, Birna Jonsdottir, Johan H. Thygesen, Adam J. Schwarz, Michael Didriksen, Tine B. Stensbøl, Michael Brammer, Shitij Kapur, Jonas G. Halldorsson, Stefan Hreidarsson, Evald Saemundsen, Engilbert Sigurdsson and Kari Stefansson ()
Additional contact information
Hreinn Stefansson: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
Andreas Meyer-Lindenberg: Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany
Stacy Steinberg: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
Brynja Magnusdottir: Landspitali, National University Hospital, IS-101 Reykjavík, Iceland
Katrin Morgen: Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany
Sunna Arnarsdottir: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
Gyda Bjornsdottir: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
G. Bragi Walters: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
Gudrun A. Jonsdottir: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
Orla M. Doyle: Institute of Psychiatry, King’s College, 16 De Crespigny Park, London SE5 8AF, UK
Heike Tost: Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany
Oliver Grimm: Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany
Solveig Kristjansdottir: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
Heimir Snorrason: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
Solveig R. Davidsdottir: Landspitali, National University Hospital, IS-101 Reykjavík, Iceland
Larus J. Gudmundsson: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
Gudbjorn F. Jonsson: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
Berglind Stefansdottir: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
Isafold Helgadottir: Landspitali, National University Hospital, IS-101 Reykjavík, Iceland
Magnus Haraldsson: Landspitali, National University Hospital, IS-101 Reykjavík, Iceland
Birna Jonsdottir: Röntgen Domus, Egilsgötu 3, IS-101 Reykjavík, Iceland
Johan H. Thygesen: Mental Health Centre Sct. Hans, Copenhagen University Hospital, Research Institute of Biological Psychiatry, Boserupvej 2, DK-4000 Roskilde, Denmark
Adam J. Schwarz: Tailored Therapeutics, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center DC 1940
Michael Didriksen: H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark
Tine B. Stensbøl: H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark
Michael Brammer: Institute of Psychiatry, King’s College, 16 De Crespigny Park, London SE5 8AF, UK
Shitij Kapur: Institute of Psychiatry, King’s College, 16 De Crespigny Park, London SE5 8AF, UK
Jonas G. Halldorsson: University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland
Stefan Hreidarsson: The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kópavogur, Iceland
Evald Saemundsen: University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland
Engilbert Sigurdsson: Landspitali, National University Hospital, IS-101 Reykjavík, Iceland
Kari Stefansson: deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland

Nature, 2014, vol. 505, issue 7483, 361-366

Abstract: 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.

Date: 2014
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DOI: 10.1038/nature12818

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