# Methods to maximize the utility of common fund functional genomic data in multi-ethnic genetic studies

> **NIH NIH R03** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $335,407

## Abstract

ABSTRACT
Smoking and drinking are major modifiable and heritable risk factors for a myriad of human diseases.
Elucidating the genetic basis for smoking and drinking addiction will be critical for public health. In the past few
years, the genetic studies of smoking and drinking addiction have made significant progress. With the help of
large datasets and advanced analytical methods, we have identified >400 associated loci in samples of European
ancestry. As a next step, we will expand our study to include samples of non-European populations, in order to
further empower discovery and elucidate the genetic architecture.
A majority of the identified GWAS loci are non-coding. A critical first step to understand their function is to
identify the target gene. Transcriptome-wide association study (TWAS) was proposed to link regulatory variants
to target genes. In its original form, TWAS integrates eQTL and GWAS data from the matched ancestry. As multi-
ethnic studies become more prevalent, it has been shown that direct integration of European eQTL with non-
European GWAS would lead to loss of power and the results may be difficult to interpret as well. A majority of
Common Funds functional genomic data (e.g., GTEx and 4DN) were primarily from European ancestry. It
remains unclear whether they remain useful in multi-ethnic studies and if so, how to effectively utilize them.
Here we propose a series of methodological innovations to combine GTEx data, epigenetic and 3D genomes data
and other non-European functional genomic data to improve the gene expression prediction accuracy across
tissue types and ancestries. For a given gene expression model, we will also propose methods to perform provably
optimal TWAS in multi-ethnic genetic studies. These proposed methods, if successful, will open doors to use
Common Funds data in the next generation genetic studies of complex traits in diverse populations. Compared
to extremely expensive data generation, these method development projects are cost effective and could be highly
impactful for maximizing the utility of Common Funds datasets.

## Key facts

- **NIH application ID:** 10357165
- **Project number:** 1R03OD032630-01
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Dajiang Liu
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $335,407
- **Award type:** 1
- **Project period:** 2021-09-22 → 2023-09-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357165

## Citation

> US National Institutes of Health, RePORTER application 10357165, Methods to maximize the utility of common fund functional genomic data in multi-ethnic genetic studies (1R03OD032630-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10357165. Licensed CC0.

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