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Mol Psychiatry. 2016 Jun;21(6):758-67. doi: 10.1038/mp.2016.45. Epub 2016 Apr 5.

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

Author information

  • 1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
  • 2Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • 3Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK.
  • 4Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
  • 5Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
  • 6Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
  • 7MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • 8Department of Psychiatry, University of Oxford, Oxford, UK.
  • 9Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
  • 10MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.

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.

PMID:
27046643
PMCID:
PMC4879186
DOI:
10.1038/mp.2016.45
[PubMed - in process]
Free PMC Article
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