# Using H-MAGMA to decipher neurobiological bases of smoking and alcohol use traits

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $237,726

## Abstract

PROJECT SUMMARY
Nicotine and alcohol dependence represent major global health concerns as leading causes of preventable
morbidity and mortality. Despite their global burden, pharmacological treatment options are limited, in large
part because their molecular mechanisms remain unclear. Cigarette smoking and alcohol use traits are
heritable, and genome-wide association studies (GWAS) have provided robust evidence for common variants
in nearly 400 genomic regions that influence smoking and/or alcohol use traits. However, the vast majority of
associated variants reside in non-coding DNA, and their target genes, gene networks, and relevant
neurobiological mechanisms are poorly understood. The critical first step of the proposal is to identify
neurobiologically-relevant target genes of known loci by applying H-MAGMA to a comprehensive set of large,
well-powered GWAS for smoking and alcohol use traits, including nicotine dependence (ND), cigarettes per
day (CPD), smoking cessation (CS), alcohol use disorder (AUD), and alcohol drinks per week (DPW). Once the
putative target genes are identified, we will characterize their (1) molecular function and biological pathways
using gene set enrichment analyses, (2) cellular expression profiles based on single cell transcriptomic
datasets, and (3) developmental expression trajectories based on temporal transcriptomic atlas. This will
refine the molecular mechanism, central cell type, and developmental window critical for using and developing
addiction to cigarette smoking and alcohol. Further, because we will use a coherent framework (H-MAGMA)
to decipher biological underpinnings of all five GWAS of smoking and alcohol use traits, our proposed study
will allow the systematic characterization and comparison of different GWAS. Our comparison will result in the
identification of pleiotropic genes associated with developing addiction to cigarette and alcohol, which would
reveal core mechanisms underlying addiction.

## Key facts

- **NIH application ID:** 10214583
- **Project number:** 5R21DA051921-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** HYEJUNG WON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $237,726
- **Award type:** 5
- **Project period:** 2020-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214583

## Citation

> US National Institutes of Health, RePORTER application 10214583, Using H-MAGMA to decipher neurobiological bases of smoking and alcohol use traits (5R21DA051921-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10214583. Licensed CC0.

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