| Application: | 16406, Causes of individual differences in cognitive and mental health |
| Title: | Conditional and interaction gene-set analysis reveals novel functional pathways for blood pressure |
| Size: | 2.0 MB |
| Archived: | 26 Nov 2020 |
| Stability: | Complete |
| Personal: | No individual-level data |
Return 2885
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Notes
Gene-set analysis provides insight into which functional and biological properties of genes are aetiologically relevant for a particular phenotype. But genes have multiple properties, and these properties are often correlated across genes. This can cause confounding in a gene-set analysis, because one property may be statistically associated even if biologically irrelevant to the phenotype, by being correlated with gene properties that are relevant. To address this issue we present a novel conditional and interaction gene-set analysis approach, which attains considerable functional refinement of its conclusions compared to traditional gene-set analysis. We applied our approach to blood pressure phenotypes in the UK Biobank data (N=360,243), the results of which we report here. We confirm and further refine several associations with multiple processes involved in heart and blood vessel formation but also identify novel interactions, among others with cardiovascular tissues involved in regulatory pathways of blood pressure homoeostasis.Application 16406
Causes of individual differences in cognitive and mental health
The main goal of our study is to quantify and understand the role of genetic variants, the environment (including lifestyle), and their interaction on outcomes related to cognitive health. In doing so we will combine expertise of statistical genetics, medical genetics, bioinformatics and functional genomics. We are specifically interested in the following health-relevant outcomes from the U.K. Biobank data: cognitive function (incl. normal function and dementia), mental health (incl. depression, neuroticism, personality, smoking, and alcohol drinking), and brain MRI. Our research will contribute to quantifying and understanding how several risk factors (e.g. lifestyle, environment, genes), both separately and in combination, influence cognitive health as well as the comorbidities between different cognitive health outcomes. Our study will consist of a combination of methods, including: - Genome-wide association studies (GWAS) that aim to identify individual genetic variants associated with a particular outcome. - Comorbidity analyses, using e.g. meta-analytic techniques, LD score regression or BOLD-GREML methods to quantify the extent of genetic overlap between particular outcomes - Gene-set analyses (e.g. using MAGMA and INRICH tools) and bioinformatic secondary analyses to understand genetic findings in terms of their biological function - Heterogeneity analyses to determine genetic subgroups of individuals - Annotation of genetic findings using external information from e.g. expression or quantitative proteomics data - Gene-by-environment correlation and interaction analyses to quantify the relevance of the interplay between genes and environment (including lifestyle) on outcomes related to cognitive health We aim to use all available observations in the UKB that are currently released and will be released in the future, and that have been successfully genotyped and have measures of relevant outcomes. ?
| Lead investigator: | Professor Danielle Posthuma |
| Lead institution: | VU University Amsterdam |
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|---|---|---|---|
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1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 2886 | Conditional and interaction gene-set analysis reveals novel functional pathways for blood pressure | Christiaan A. de Leeuw (+4) | 2018 | Nature Communications |
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