Publication Date:
2013-12-20
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stefansson, Hreinn -- Meyer-Lindenberg, Andreas -- Steinberg, Stacy -- Magnusdottir, Brynja -- Morgen, Katrin -- Arnarsdottir, Sunna -- Bjornsdottir, Gyda -- Walters, G Bragi -- Jonsdottir, Gudrun A -- Doyle, Orla M -- Tost, Heike -- Grimm, Oliver -- Kristjansdottir, Solveig -- Snorrason, Heimir -- Davidsdottir, Solveig R -- Gudmundsson, Larus J -- Jonsson, Gudbjorn F -- Stefansdottir, Berglind -- Helgadottir, Isafold -- Haraldsson, Magnus -- Jonsdottir, Birna -- Thygesen, Johan H -- Schwarz, Adam J -- Didriksen, Michael -- Stensbol, Tine B -- Brammer, Michael -- Kapur, Shitij -- Halldorsson, Jonas G -- Hreidarsson, Stefan -- Saemundsen, Evald -- Sigurdsson, Engilbert -- Stefansson, Kari -- G0701748/Medical Research Council/United Kingdom -- England -- Nature. 2014 Jan 16;505(7483):361-6. doi: 10.1038/nature12818. Epub 2013 Dec 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavik, Iceland [2]. ; 1] Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany [2]. ; deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavik, Iceland. ; Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavik, Iceland. ; Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany. ; 1] deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavik, Iceland [2] Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavik, Iceland. ; Institute of Psychiatry, King's College, 16 De Crespigny Park, London SE5 8AF, UK. ; 1] Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavik, Iceland [2] University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland. ; Rontgen Domus, Egilsgotu 3, IS-101 Reykjavik, 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. ; University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland. ; The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kopavogur, Iceland. ; 1] University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland [2] The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kopavogur, Iceland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24352232" target="_blank"〉PubMed〈/a〉
Keywords:
Adolescent
;
Adult
;
Aged
;
Autistic Disorder/*genetics
;
Brain/abnormalities/anatomy & histology/metabolism
;
Case-Control Studies
;
Chromosome Deletion
;
Chromosomes, Human/genetics
;
Chromosomes, Human, Pair 15/genetics
;
Cognition/*physiology
;
DNA Copy Number Variations/*genetics
;
Dyslexia/genetics
;
Female
;
Fertility/genetics
;
*Genetic Predisposition to Disease
;
Heterozygote
;
Humans
;
Iceland
;
Learning Disorders/genetics
;
Magnetic Resonance Imaging
;
Male
;
Middle Aged
;
Neuropsychological Tests
;
Phenotype
;
Schizophrenia/*genetics
;
Young Adult
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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