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

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


Author 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.
Deary, I. J.
Title Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)
Formatted title
Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1476-5578
1359-4184
Publication date 2016-04-05
Year available 2016
Sub-type Article (original research)
DOI 10.1038/mp.2016.45
Open Access Status DOI
Volume 21
Start page 758
End page 767
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Formatted 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 the ATXN2, 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.
Keyword Cognitive functions
Mental and physical well-being
Psychiatric disorders
Physical illness
Single-nucleotide polymorphisms (SNPs)
Genetic variation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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