Altmetric

Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease

File Description SizeFormat 
MAIN_TEXT_TABLES _METHODS_25NOV15.docxAccepted version358.56 kBMicrosoft WordView/Open
Title: Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease
Authors: Johnson, MR
Shkura, K
Langley, SR
Delahaye-Duriez, A
Srivastava, P
Hill, WD
Rackham, OJL
Davies, G
Harris, SE
Moreno-Moral, A
Rotival, M
Speed, D
Petrovski, S
Katz, A
Hayward, C
Porteous, DJ
Smith, BH
Padmanabhan, S
Hocking, LJ
Starr, JM
Liewald, DC
Visconti, A
Falchi, M
Bottolo, L
Rossetti, T
Danis, B
Mazzuferi, M
Foerch, P
Grote, A
Helmstaedter, C
Becker, AJ
Kaminski, RM
Deary, IJ
Petretto, E
Item Type: Journal Article
Abstract: Genetic determinants of cognition are poorly characterized, and their relationship to genes that confer risk for neurodevelopmental disease is unclear. Here we performed a systems-level analysis of genome-wide gene expression data to infer gene-regulatory networks conserved across species and brain regions. Two of these networks, M1 and M3, showed replicable enrichment for common genetic variants underlying healthy human cognitive abilities, including memory. Using exome sequence data from 6,871 trios, we found that M3 genes were also enriched for mutations ascertained from patients with neurodevelopmental disease generally, and intellectual disability and epileptic encephalopathy in particular. M3 consists of 150 genes whose expression is tightly developmentally regulated, but which are collectively poorly annotated for known functional pathways. These results illustrate how systems-level analyses can reveal previously unappreciated relationships between neurodevelopmental disease–associated genes in the developed human brain, and provide empirical support for a convergent gene-regulatory network influencing cognition and neurodevelopmental disease.
Issue Date: 27-Jan-2016
Date of Acceptance: 15-Nov-2015
URI: http://hdl.handle.net/10044/1/30333
DOI: https://dx.doi.org/10.1038/nn.4205
ISSN: 1546-1726
Publisher: Nature Publishing Group
Start Page: 223
End Page: 232
Journal / Book Title: Nature Neuroscience
Volume: 19
Issue: 2
Copyright Statement: © 2016 Nautre America, Inc. All rights reserved.
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
UCB PHARMA SA
Funder's Grant Number: RDA03
RD610
P35076
4500301248
Keywords: Science & Technology
Life Sciences & Biomedicine
Neurosciences
Neurosciences & Neurology
DE-NOVO MUTATIONS
GENOME-WIDE ASSOCIATION
SCOTTISH FAMILY HEALTH
HUMAN BRAIN
EPILEPTIC ENCEPHALOPATHIES
INTELLECTUAL DISABILITY
GENERATION SCOTLAND
HUMAN INTELLIGENCE
TEST BATTERIES
SET ANALYSIS
Animals
Brain Chemistry
Cognition
Developmental Disabilities
Epilepsy, Temporal Lobe
Gene Expression
Gene Regulatory Networks
Genetic Variation
Genome-Wide Association Study
Hippocampus
Humans
Nervous System
Synapses
Neurology & Neurosurgery
1109 Neurosciences
1702 Cognitive Science
Publication Status: Published
Appears in Collections:Clinical Sciences
Molecular Sciences
Department of Medicine
Faculty of Medicine



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commonsx