| Application: | 10279, The relationship of cognitive function and negative emotions with morbidity and mortality: an aetiological investigation |
| Title: | Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions |
| Size: | 299499 B |
| Archived: | 17 Oct 2017 |
| Stability: | Complete |
| Personal: | No individual-level data |
Return 762
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Notes
Differences in general cognitive function have been shown to be partly heritable and to show genetic correlations with several psychiatric and physical disease states. However, to date, few single-nucleotide polymorphisms (SNPs) have demonstrated genome-wide significance, hampering efforts aimed at determining which genetic variants are most important for cognitive function and which regions drive the genetic associations between cognitive function and disease states. Here, we combine multiple large genome-wide association study (GWAS) data sets, from the CHARGE cognitive consortium (n = 53 949) and UK Biobank (n = 36 035), to partition the genome into 52 functional annotations and an additional 10 annotations describing tissuespecific histone marks. Using stratified linkage disequilibrium score regression we show that, in two measures of cognitive function, SNPs associated with cognitive function cluster in regions of the genome that are under evolutionary negative selective pressure. These conserved regions contained ~ 2.6% of the SNPs from each GWAS but accounted for ~ 40% of the SNP-based heritability. The results suggest that the search for causal variants associated with cognitive function, and those variants that exert a pleiotropic effect between cognitive function and health, will be facilitated by examining these enriched regions.WD Hill, et al.Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions Translational Psychiatry (2016) 6, e980; doi:10.1038/tp.2016.246;
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 |
|---|---|---|---|---|
| 763 | Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions | W D Hill (+7) | 2016 | Translational Psychiatry |
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