Determinants and Mechanisms Involved in Alcohol Consumption and its Health Consequences
Lead Research Organisation:
Brunel University London
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

Elliott P
(2020)
Estimated 24-Hour Urinary Sodium Excretion and Incident Cardiovascular Disease and Mortality Among 398 628 Individuals in UK Biobank.
in Hypertension (Dallas, Tex. : 1979)

Evangelou E
(2021)
Alcohol consumption in the general population is associated with structural changes in multiple organ systems.
in eLife

Hezekiah C
(2024)
Physical activity alters the effect of genetic determinants of adiposity on hypertension among individuals of European ancestry in the UKB.
in Scandinavian journal of medicine & science in sports

Jiang X
(2022)
Urinary Sodium Excretion Enhances the Effect of Alcohol on Blood Pressure.
in Healthcare (Basel, Switzerland)

O'Farrell F
(2023)
Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis.
in Scientific reports

O'Farrell F
(2022)
Molecular Alterations Caused by Alcohol Consumption in the UK Biobank: A Mendelian Randomisation Study.
in Nutrients

Pazoki R
(2021)
Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.
in Nature communications


Pazoki R
(2021)
Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.
in Nat Commun

Roa-Díaz ZM
(2021)
Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study.
in Journal of clinical medicine
Related Projects
Project Reference | Relationship | Related To | Start | End | Award Value |
---|---|---|---|---|---|
MR/R026505/1 | 01/02/2018 | 09/02/2020 | £484,175 | ||
MR/R026505/2 | Transfer | MR/R026505/1 | 31/05/2020 | 29/06/2022 | £292,652 |
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. ftp://ftp.ebi.ac.uk/pub/databases/gwas/summary_statistics/GCST90013405 ftp://ftp.ebi.ac.uk/pub/databases/gwas/summary_statistics/GCST90013406 ftp://ftp.ebi.ac.uk/pub/databases/gwas/summary_statistics/GCST90013407 |
URL | http://ftp://ftp.ebi.ac.uk/pub/databases/gwas/summary_statistics/GCST90013405 |
Description | Collaboration with Division of Sport, Health and Exercise Sciences 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 Division of Sport, Health and Exercise Sciences 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 | Collaboration with University of Liverpool |
Organisation | University of Liverpool |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Investigation of the effect of alcohol on C. elegans. |
Collaborator Contribution | The partner has contributed the work to order and perform the experiments on C.elegans. |
Impact | The work is ongoing and we have still not received any results. |
Start Year | 2021 |
Description | Genome-wide association study and replication of liver enzyme loci |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | A presentation in the European Society of human Genetics about our research on genetic analysis of liver enzymes. |
Year(s) Of Engagement Activity | 2021 |
URL | https://2021.eshg.org/programme/sunday-june-13-virtual-conference/ |
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 | Percentage of explained variance in alcohol consumption by genetic risk score in the UK Biobank |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | This is an ePoster presentation for the European Society of Human Genetics 2021. Your e-Poster: P19.025.A - Percentage of explained variance in alcohol consumption by genetic risk score in the UK Biobank e-Poster Viewing with Authors: Group A Saturday, June 12, 2021, 14.45 - 15.30 hrs CEST (Central European Summer Time!) |
Year(s) Of Engagement Activity | 2021 |
URL | https://2021.eshg.org/programme/saturday-june-12-virtual-conference/ |
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 |