@article{0c653769a2ee46a5b2c26be6c9e82a82,
title = "Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)",
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.",
keywords = "Genetics, Psychology",
author = "G. Davies and Marioni, {R. E.} and Liewald, {D. C.} and Hill, {W. D.} and Hagenaars, {S. P.} and Harris, {S. E.} and Ritchie, {S. J.} and M. Luciano and C. Fawns-Ritchie and D. Lyall and B. Cullen and Cox, {S. R.} and C. Hayward and Porteous, {D. J.} and J. Evans and McIntosh, {A. M.} and J. Gallacher and N. Craddock and Pell, {J. P.} and Smith, {D. J.} and Gale, {C. R.} and Deary, {I. J.}",
note = "Publisher Copyright: {\textcopyright} 2016 Macmillan Publishers Limited. This research was conducted, using the UK Biobank Resource, in The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council 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. GS 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 GS 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. Data collection from the Lothian Birth Cohort 1936 (LBC1936) was supported by the Disconnected Mind project, funded by Age UK. We thank the LBC1936 members for their participation, and the whole LBC1936 team for their work on the phenotypes. BBSRC provided funding for the genetic testing in LBC1936 (BB/F019394/1). Genotyping was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility (WTCRF), Edinburgh, Scotland, funded by the MRC. We thank the Scottish Council for Research in Education Centre, University of Glasgow, for access to the results from the Scottish Mental Survey 1947. We are grateful for the use of summary data from a subset of cohorts included in the CHARGE consortium cognitive working group general cognitive function GWAS (see Supplementary Methods).",
year = "2016",
month = jun,
day = "1",
doi = "10.1038/mp.2016.45",
language = "English",
volume = "21",
pages = "758--767",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "6",
}
