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. 2014 Jan 16;505(7483):361-6.
doi: 10.1038/nature12818. Epub 2013 Dec 18.

CNVs conferring risk of autism or schizophrenia affect cognition in controls

Hreinn Stefansson  1 , Andreas Meyer-Lindenberg  2 , Stacy Steinberg  3 , Brynja Magnusdottir  4 , Katrin Morgen  5 , Sunna Arnarsdottir  6 , Gyda Bjornsdottir  3 , G Bragi Walters  3 , Gudrun A Jonsdottir  3 , Orla M Doyle  7 , Heike Tost  5 , Oliver Grimm  5 , Solveig Kristjansdottir  3 , Heimir Snorrason  3 , Solveig R Davidsdottir  4 , Larus J Gudmundsson  3 , Gudbjorn F Jonsson  3 , Berglind Stefansdottir  3 , Isafold Helgadottir  4 , Magnus Haraldsson  8 , Birna Jonsdottir  9 , Johan H Thygesen  10 , Adam J Schwarz  11 , Michael Didriksen  12 , Tine B Stensbøl  12 , Michael Brammer  7 , Shitij Kapur  7 , Jonas G Halldorsson  13 , Stefan Hreidarsson  14 , Evald Saemundsen  15 , Engilbert Sigurdsson  8 , Kari Stefansson  3
Affiliations

CNVs conferring risk of autism or schizophrenia affect cognition in controls

Hreinn Stefansson et al. Nature. .

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.

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