Journal article
Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease
MR Johnson, K Shkura, SR Langley, A Delahaye-Duriez, P Srivastava, WD Hill, OJL Rackham, G Davies, SE Harris, A Moreno-Moral, M Rotival, D Speed, S Petrovski, A Katz, C Hayward, DJ Porteous, BH Smith, S Padmanabhan, LJ Hocking, JM Starr Show all
Nature Neuroscience | Published : 2016
DOI: 10.1038/nn.4205
Abstract
© 2016 Nature America, Inc. All rights reserved. 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 d..
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Awarded by Age UK
Funding Acknowledgements
We acknowledge funding from UK Imperial National Institute for Health Research Biomedical Research Centre (M.R.J.), the UK Medical Research Council (M.R.J., E.P. and D.S.), The National Genome Research Network (NGFNplus: EMINet, grant 01GS08122; A.J.B.), EuroEpinomics (A.J.B.), UCB Pharma (M.R.J. and E.P.) and the Singapore Ministry of Health (E.P.). We thank the Lothian Birth Cohort 1936 research team for data collection and collation. The Lothian Birth Cohort 1936 is supported by Age UK (Disconnected Mind project). The work at The University of Edinburgh was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). We acknowledge funding from the Biotechnology and Biological Sciences Research Council and MRC. Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorate CZD/16/6 and the Scottish Funding Council HR03006. Genotyping of the GS:SFHS samples was carried out by staff at the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the UK's Medical Research Council. We thank all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants and nurses. A.D.-D. was supported by a Marie Curie Intra European Fellowship within the 7th European Community Framework Programme.