People s differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genomewide 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 frequency40.01), 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.
G Davies, et al. Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112151). Molecular Psychiatry (2016) 21, 758 767; doi:10.1038/mp.2016.45
The relationship of cognitive function and negative emotions with morbidity and mortality: an aetiological investigation
To understand why poorer cognitive function and negative emotional factors are typically associated with poorer health and increased mortality.
The explanation for the associations between poorer cognitive function or negative emotions and adverse health outcomes are unclear. In general, adjustment for potentially confounding or mediating factors has had little attenuating effect on the associations, but many studies have lacked comprehensive data on such factors. It is important that we investigate the biological determinants of the relationships between cognitive function and negative emotional states and traits, and later health outcomes. Publications:
1. G Davies, et al. Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112151)
2. WD Hill, et al.Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions
|Lead investigator:||Catharine Gale|
|Lead institution:||University of Edinburgh|
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