• 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.
• 1] deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland [2].
• Nature. 2014 Jan 16;505(7483):361-6.

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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