CNVs conferring risk of autism or schizophrenia affect cognition in controls

@article{Stefnsson2014CNVsCR,
  title={CNVs conferring risk of autism or schizophrenia affect cognition in controls},
  author={Hreinn Stef{\'a}nsson and Andreas Meyer-Lindenberg and Stacy Steinberg and Brynja B Magnusdottir and Katrin Morgen and Sunna Arnarsd{\'o}ttir and Gyda Bjornsdottir and G. Bragi Walters and Gudrun A. Jonsdottir and Orla M. Doyle and Heike Tost and Oliver Grimm and Solveig Kristjansdottir and Heimir Snorrason and Solveig Davidsdottir and L{\'a}rus J. Gudmundsson and Gudbjorn F. Jonsson and Berglind Stef{\'a}nsd{\'o}ttir and Isafold Helgadottir and Magn{\'u}s Haraldsson and Birna Gerður J{\'o}nsd{\'o}ttir and Johan H. Thygesen and Adam J. Schwarz and Michael Didriksen and Tine Bryan Stensb{\o}l and Michael J. Brammer and Shitij Kapur and J{\'o}nas G. Halld{\'o}rsson and Stef{\'a}n J Hreidarsson and Evald Saemundsen and Engilbert Sigurdsson and K{\'a}ri Stef{\'a}nsson},
  journal={Nature},
  year={2014},
  volume={505},
  pages={361-366}
}
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… 
Appreciating the Population-wide Impact of Copy Number Variants on Cognition
TLDR
The impact of CNVs, discovered with genotyping arrays, in over 150,000 mostly unaffected individuals by assessing scores from multiple cognitive tests is investigated, finding 12 CNVs can be considered as mutational hotspots with comparatively high population frequencies for a given relative risk, resulting in sufficient power to detect schizophrenia association.
Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study
TLDR
The findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk.
Cross-Disorder Comparison of Four Neuropsychiatric CNV Loci
TLDR
This review describes the phenotypes and syndromic features associated with CNVs at four of the best-characterized risk loci for neuropsychiatric disorders and demonstrates a pattern of asymmetric shared risk in which CNVs increase the risk of multiple disorders but to differing degrees.
Unraveling the genetic architecture of copy number variants associated with schizophrenia and other neuropsychiatric disorders
TLDR
The genomic data connecting CNVs with a multitude of human neuropsychiatric disease, the current technical ability to model such chromosomal anomalies in mouse, and the existence of precise behavioral measures of endophenotypes argue that the time is ripe for systematic dissection of the genetic mechanisms underlying such disease.
Genomics of schizophrenia
TLDR
This chapter reviews the genetic epidemiology of schizophrenia, and how recent genome-wide association studies, other array-based methods, and genome sequencing are helping to re-conceptualize the condition.
Use of mouse models to investigate the contributions of CNVs associated with schizophrenia and autism to disease mechanisms.
  • S. Hyman
  • Medicine
    Current opinion in genetics & development
  • 2021
TLDR
This work focuses on the translational utility of transgenic mice that carry models of human neuropsychiatric CNVs, while recognizing their limitations as veridical models of complex human brain disorders.
Rare Copy Number Variants Are Associated With Poorer Cognition in Schizophrenia
TLDR
In those with schizophrenia, cognitive ability in schizophrenia CNV carriers is 0.5-1.0 standard deviations below non-CNV carriers, which may have implications for clinical assessment and management.
Effects of eight neuropsychiatric copy number variants on human brain structure
TLDR
Although CNVs mainly showed distinct brain patterns, principal component analysis loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps.
Investigation of the genetic basis of schizophrenia and cognitive function
TLDR
Three genes identified in the first study (SATB2, BCL11B and GATAD2A) that regulate stages of neurodevelopment via epigenetic mechanisms are investigated, which are a heritable means of regulating various genomic functions to orchestrate processes such as brain development.
Genetic Causes and Modifiers of Autism Spectrum Disorder
TLDR
The genetic landscape of ASD is described and it is discussed how genetic modifiers such as copy number variation, single nucleotide polymorphisms, and epigenetic alterations likely play a key role in modulating the phenotypic spectrum of ASD patients.
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