| Application: | 10279, The relationship of cognitive function and negative emotions with morbidity and mortality: an aetiological investigation |
| Title: | The influence of X chromosome variants on trait neuroticism |
| Size: | 1.4 MB |
| Archived: | 9 Mar 2021 |
| Stability: | Complete |
| Personal: | No individual-level data |
Return 3184
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Notes
Autosomal variants have successfully been associated with trait neuroticism in genome-wide analysis of adequately-powered samples. But such studies have so far excluded the X chromosome from analysis. Here, we report genetic association analyses of X chromosome and XY pseudoautosomal single nucleotide polymorphisms (SNPs) and trait neuroticism using UK Biobank samples (N = 405,274). Significant association was found with neuroticism on the X chromosome for 204 markers found within three independent loci (a further 783 were suggestive). Most of these significant neuroticism-related X chromosome variants were located in intergenic regions (n = 713). Involvement of HS6ST2, which has been previously associated with sociability behaviour in the dog, was supported by single SNP and gene-based tests. We found that the amino acid and nucleotide sequences are highly conserved between dogs and humans. From the suggestive X chromosome variants, there were 19 nearby genes which could be linked to gene ontology information. Molecular function was primarily related to binding and catalytic activity; notable biological processes were cellular and metabolic, and nucleic acid binding and transcription factor protein classes were most commonly involved. X-variant heritability of neuroticism was estimated at 0.22% (SE = 0.05) from a full dosage compensation model. A polygenic X-variant score created in an independent sample (maximum N ≅ 7300) did not predict significant variance in neuroticism, psychological distress, or depressive disorder. We conclude that the X chromosome harbours significant variants influencing neuroticism, and might prove important for other quantitative traits and complex disorders.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 |
|---|---|---|---|---|
| 3185 | The influence of X chromosome variants on trait neuroticism | Michelle Luciano (+9) | 2019 | Molecular Psychiatry |
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