UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability

Singh, T; Walters, JTR; Johnstone, M; Curtis, D; Suvisaari, J; Torniainen, M; Rees, E; ... Barrett, JC; + view all (2017) The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability. Nature Genetics , 49 pp. 1167-1173. 10.1038/ng.3903. Green open access

[img]
Preview
Text
Singh-Bramon accepted 46167_2 CNVS in schiz and LD.pdf - Accepted version

Download (812kB) | Preview

Abstract

By performing a meta-analysis of rare coding variants in whole-exome sequences from 4,133 schizophrenia cases and 9,274 controls, de novo mutations in 1,077 family trios, and copy number variants from 6,882 cases and 11,255 controls, we show that individuals with schizophrenia carry a significant burden of rare, damaging variants in 3,488 genes previously identified as having a near-complete depletion of loss-of-function variants. In patients with schizophrenia who also have intellectual disability, this burden is concentrated in risk genes associated with neurodevelopmental disorders. After excluding known risk genes for neurodevelopmental disorders, a significant rare variant burden persists in other genes intolerant of loss-of-function variants; although this effect is notably stronger in patients with both schizophrenia and intellectual disability, it is also seen in patients with schizophrenia who do not have intellectual disability. Together, our results show that rare, damaging variants contribute to the risk of schizophrenia both with and without intellectual disability and support an overlap of genetic risk between schizophrenia and other neurodevelopmental disorders.

Type: Article
Title: The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ng.3903
Publisher version: http://dx.doi.org/10.1038/ng.3903
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: DNA sequencing, Neurodevelopmental disorders, Schizophrenia
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/1560304
Downloads since deposit
170Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item