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.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: G
authors.initials: G
authors.lastname: Davies
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK.|Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: R E
authors.initials: RE
authors.lastname: Marioni
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Liewald
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: W D
authors.initials: WD
authors.lastname: Hill
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.|Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Hagenaars
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK.
authors.forename: S E
authors.initials: SE
authors.lastname: Harris
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Ritchie
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: M
authors.initials: M
authors.lastname: Luciano
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: C
authors.initials: C
authors.lastname: Fawns-Ritchie
authors.affiliation: Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
authors.forename: D
authors.initials: D
authors.lastname: Lyall
authors.affiliation: Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
authors.forename: B
authors.initials: B
authors.lastname: Cullen
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Cox
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: C
authors.initials: C
authors.lastname: Hayward
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Porteous
authors.affiliation: Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
authors.forename: J
authors.initials: J
authors.lastname: Evans
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: McIntosh
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: J
authors.initials: J
authors.lastname: Gallacher
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
authors.forename: N
authors.initials: N
authors.lastname: Craddock
authors.affiliation: Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Pell
authors.affiliation: Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Smith
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.|MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
authors.forename: C R
authors.initials: CR
authors.lastname: Gale
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: I J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000368:Aged; D018070:Biological Specimen Banks; D003071:Cognition / Q000502:physiology*; D004522:Educational Status; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D006113:United Kingdom