| Application: | 10279, The relationship of cognitive function and negative emotions with morbidity and mortality: an aetiological investigation |
| Title: | Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112151) |
| Size: | 1.1 GB |
| Archived: | 17 Oct 2017 |
| Stability: | Complete |
| Personal: | No individual-level data |
Return 760
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Notes
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
Application 10279
The relationship of cognitive function and negative emotions with morbidity and mortality: an aetiological investigation
The proposed research aims to understand why it is that poorer cognitive function and negative emotional factors are typically associated with poorer health and increased mortality. We shall use health outcome data to examine how all-cause mortality and incident cancer and cardiovascular disease (CVD)vary according to prior cognitive function and negative emotions. We shall investigate the extent to which relationships we find between cognition, emotions and these health outcomes are explained or modified by physical, biological, genetic, behavioural, and socio-demographic factors. Genetic analyses will incorporate multivariate genome-wide complex trait analysis and polygenic prediction of these relationships. Poorer cognitive function and negative emotional states and traits have been shown to increase mortality but the reasons for this are unclear. We anticipate that the proposed research will: 1) show us how mortality and morbidity from common health conditions vary according to prior cognitive abilities and emotional factors; 2) reveal potential mechanisms whereby poorer cognition and negative emotion increase risk; and 3) identify whether other characteristics can increase or reduce the risk of ill health in those with poorer cognition and negative emotions. This information could help inform intervention strategies for preventing or treating common health conditions. Using data on cognitive function and negative emotions together with data collected on health outcomes, scientists at the Centre for Cognitive Ageing and Cognitive Epidemiology will examine whether cognitive performance and emotional states predict risk of all-cause mortality and the onset of cancer and CVD. They will investigate whether other characteristics, such as lifestyle, socio-demographic, physical, behavioural or biological factors, help to explain any links between cognitive function and emotions and these health outcomes. They will estimate degree of genetic sharing between: 1) cognitive function/emotions and these characteristics, and 2) cognitive function/emotions and health outcomes. The full cohort
| Lead investigator: | Dr Michelle Luciano |
| Lead institution: | University of Edinburgh |
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1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 761 | Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151) | G Davies (+21) | 2016 | Molecular Psychiatry |
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