Determinants and Mechanisms Involved in Alcohol Consumption and its Health Consequences

Lead Research Organisation: Brunel University
Department Name: Life Sciences

Abstract

In the current proposed research, I will be using genetic, environmental and metabolite data from the UK Biobank, the Airwave health monitoring study and published genome-wide association studies as well as animal models in order to highlight determinants, mechanisms and pathways involved in alcohol consumption and related diseases. I will use UK Biobank data to study risk factors and determinants of alcohol consumption as well as diseases caused by alcohol consumption. By using alcohol consumption data and metabolites in the Airwave study, I will identify genes that are linked to alcohol-related metabolites. I will then test alcohol-metabolite genes in the UK Biobank study to highlight pathways that are linked to fat accumulation in liver via alcohol consumption. I will additionally test animal models to identify the underlying biology behind the association of genes and alcohol consumption.

Technical Summary

Here, I propose to use genetic and phenotype data to systematically explore genetic and environmental factors as well as gene-environment interactions involved in alcohol consumption and alcohol induced latent changes in liver. I will use large-scale genetic and phenotype data from the UK Biobank study and he Airwave health monitoring study. I will validate the results in collaboration with universities of Liverpool and Leicester. My main aim is to unravel mechanisms involved in alcohol consumption and its consequences. I specifically aim to identify (1) phenotypic and genetic determinants and gene-environment interactions involved in alcohol consumption and its related disease. Here, I will use UK biobank study data and agnostically identify phenotypes associated with alcohol consumption. I will additionally select alcohol-related genetic variants from existing literature and identify phenotypes associated with selected genes in the UK Biobank and consequently test gene-environment interactions. (2) Identify biologic mechanisms involved in alcohol consumption using animal models. This will be done in collaboration with universities of Liverpool and Leicester (3) Identify pathways involved in fat accumulation in liver. Here, I will use metabolites from the Airwave study to identify alcohol-related metabolites. Consequently using the Airwave study, I will identify genes associated with alcohol-related metabolites for further investigation using the UK Biobank genetic and imaging data, to identify pathways involved in fat accumulation in liver through alcohol consumption. (4) Highlight brain areas involved in alcohol consumption using bioinformatics approaches in combination with brain imaging and genetic data (5) Identify novel outcomes caused by alcohol consumption. Here, I will use Mendelian Randomization (MR) study to investigate causality between alcohol consumption with related diseases.

Publications

10 25 50
 
Title GWAS Liver Enzyme 
Description Genome -wide association study for serum level of liver enzymes were performed and the summary statistics was made publicly available. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact This database is made available on the GWAS Catalog website which is a repository for the GWAs performed worldwide to date. This data has free global access by scientists and the results will be used by various scientists for various kind of research looking into using genetic underpinning of serum level of liver enzymes. 
 
Description Collaboration with Behrooz Alizadeh lab in Groningen, the Netherlands 
Organisation University of Groningen
Country Netherlands 
Sector Academic/University 
PI Contribution We provide genetic variants we identified for increase in the level of liver enzymes.
Collaborator Contribution The collaborators replicates the associations in three cohorts from the Lifelines Study.
Impact Manuscript in preparation
Start Year 2020
 
Description Collaboration with Dr Daniel Bailey at Brunel University, London 
Organisation Brunel University London
Department Department of Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Dr Daniel Bailey has quantitative expertise in physical activity data specifically reading and interpretation of accelerometer data that is useful in identification of interactions with alcohol consumption.
Collaborator Contribution My partner has agreed to help me with interpretation of accelerometer data within the UK Biobank in order to identify associations and interactions with alcohol consumption in relation to diseases.
Impact The collaboration has just commenced and not yet resulted in any outputs.
Start Year 2020
 
Description Collaboration with MRC Toxicology Unit Cambridge 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution joined recruitment of staff to perform Drosophila models.
Collaborator Contribution Mentorship and recruitment of staff member.
Impact Research Agreement has been signed off.
Start Year 2021
 
Description Longitudinal Studies Conference 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Scientists working with longitudinal studies to be gathered in this conference. Our project on phenome-wide association analysis of alcohol consumption is accepted for a poster presentation and lightning talk and the presentations are already submitted to be presented virtually.
Year(s) Of Engagement Activity 2021
 
Description Poster Presentation and lightning talk- Longitudinal Studies Conference 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Scientists working with longitudinal studies to be gathered in this conference. Our project on gene score of alcohol consumption and risk of cardiovascular diseases is accepted for a poster presentation and lightning talk and the presentations are already submitted to be presented virtually.
Year(s) Of Engagement Activity 2021