Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)

Davies, G. et al. (2016) Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151). Molecular Psychiatry, 21, pp. 758-767. (doi:10.1038/mp.2016.45)

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Abstract

People’s differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal–numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in theATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31%(s.e.m.=1.8%) for verbal–numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer’s disease and schizophrenia.

Item Type:Articles
Additional Information:This research was conducted, using the UK Biobank Resource, in The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the crosscouncil Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. Generation Scotland has received core funding from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). We are grateful to 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. Genotyping was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility (WTCRF), Edinburgh, Scotland, funded by the MRC. The Quantitative Trait Locus team at the Human Genetics Unit are funded by the MRC.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Evans, Professor Jonathan and Cullen, Dr Breda and Smith, Professor Daniel and Pell, Professor Jill and Lyall, Dr Donald
Authors: Davies, G., Marioni, R.E., Liewald, D.C., Hill, W.D., Hagenaars, S.P., Harris, S.E., Ritchie, S.J., Luciano, M., Fawns-Ritchie, C., Lyall, D., Cullen, B., Cox, S.R., Hayward, C., Porteous, D.J., Evans, J., McIntosh, A.M., Gallacher, J., Craddock, N., Pell, J.P., Smith, D.J., Gale, C.R., and Deary, I.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
Journal Name:Molecular Psychiatry
Publisher:Nature Publishing Group
ISSN:1359-4184
ISSN (Online):1476-5578
Published Online:05 April 2016
Copyright Holders:Copyright © 2016 Macmillan Publishers
First Published:First published in Molecular Psychiatry 21:758-767
Publisher Policy:Reproduced under a creative commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
381724Generation ScotlandAnna DominiczakScottish Executive Health Department (SEHHD-CSO)CZD/16/6RI CARDIOVASCULAR & MEDICAL SCIENCES