# Trans-omic Analysis of Alcohol Consumption and its Relation to Cardiovascular Disease

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $543,569

## Abstract

PROJECT SUMMARY
Alcohol consumption is an important modifiable lifestyle risk factor for cardiovascular disease (CVD). Advances
in high-throughput technologies have made it possible to measure and analyze a variety of ‘omics’, that is, DNA
methylation (methylome), gene expression (transcriptome), protein (proteome) and metabolite (metabolome), in
relation to alcohol consumption and CVD in a cost-efficient manner. In this grant proposal, we will test the
hypothesis that alcohol consumption alters multiple molecular processes across different “omics” dimensions
and these molecular intermediates mediate alcohol’s effects on CVD.
To test this hypothesis, we will assemble a multidisciplinary team to test five Specific Aims. In Aim 1, we will first
identify alcohol-associated transcriptomic markers. We will then examine the associations of alcohol-associated
transcriptomic markers with incident CVD (fatal and nonfatal coronary heart disease and ischemic stroke), and
test whether these transcriptomic markers mediate the effect of alcohol intake on incident CVD. We will construct
polygenic risk scores to examine the potential causal relationships between alcohol intake, transcriptomic
markers, and incident CVD. We will also conduct a two-sample Mendelian randomization (MR) analysis to further
test and quantify the causal relationships. In Aims 2 and 3, we will identify alcohol-associated proteomic (Aim 2)
and metabolomic (Aim 3) markers and will test the relationship between alcohol, omics markers and CVD using
similar methods outlined in Aim 1. Many alcohol-associated DNA methylation markers have been identified by
our prior study in >13,000 participants. Therefore, in Aim 4, we will examine the relations of alcohol-associated
DNA methylation markers with incident CVD using similar methods outlined in Aim 1. In Aim 5, we will integrate
alcohol-associated multi-omics markers to identify key pathways and multi-omics modules associated with
alcohol intake and CVD. We will perform Random Forest analysis to identify additional alcohol-associated multi-
omics markers. We will also perform network analyses to identify modules of alcohol-associated multi-omics
markers. We will examine the relationships between these identified multi-omics markers with incident CVD, and
will functionally annotate these markers using bioinformatics tools (e.g., ENCODE, GTEx, Human Metabolome
Database, and UniProt). With the completion of this project, we will highlight the novel molecular targets for both
alcohol-associated CVD risk prevention and treatment. In addition, we will generate a multi-omics biomarker
database of alcohol intake with tailored software to facilitate the future investigations of alcohol’s relations with
other non-communicable diseases such as neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10436830
- **Project number:** 5R01AA028263-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Chunyu Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $543,569
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436830

## Citation

> US National Institutes of Health, RePORTER application 10436830, Trans-omic Analysis of Alcohol Consumption and its Relation to Cardiovascular Disease (5R01AA028263-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436830. Licensed CC0.

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