# Improving cross ancestry polygenic prediction of tobacco and alcohol use

> **NIH NIH K01** · UNIVERSITY OF MINNESOTA · 2024 · $160,119

## Abstract

Project Summary/Abstract
Tobacco and alcohol are the most commonly used substances of abuse, resulting in heavy personal and public
health costs. The ability to identify risk prior to substance initiation has important potential to inform prevention
efforts and tailor more effective treatments through precision medicine approaches. Continuing technological
progress and reduced costs of genotyping have resulted in very large sample sizes in genetic association
studies, findings of which have allowed for the prediction of individual genetic risk, through polygenic risk scores.
These results have ignited interest in the use of polygenic scores to inform personalized prevention efforts,
population-level screening, and as statistical controls or genetic instruments within research. The incorporation
of polygenic scores in clinical and research settings shows promise, however there are several limitations to their
current use including modest predictive accuracy and limited portability across populations. The proposed
research will leverage a trans-ancestry genome-wide association study of tobacco and alcohol use in 3.4 million
individuals, combined with ~2.5 million additional participants with microarray, exome, or whole-genome
sequencing data to improve polygenic prediction of substance use behaviors and to maximize predictive
accuracy of such scores across individuals of diverse genetic ancestries. There are two major research aims: 1)
to pool large cohorts of diverse ancestry genetic studies that include information on common and rare genetic
variation, and gene expression, to improve genomic risk prediction for substance use, and 2) evaluate and
correct for the sources of reduced cross-ancestry portability of polygenic scores in order to increase their utility
with higher predictive accuracy across all genetic ancestries. To accomplish these research aims and to achieve
the goal of an independent research career, this proposal includes new mentored training in 1) advanced and
functional genomics, 2) advanced statistic and population genetics, 3) ethical, legal, and social implications
(ELSI) of genetic research. This proposal directly aligns with NIDA’s goals to identify the genetic mechanisms
that influence substance use and to use this research to address health disparities. The candidate will receive
extensive mentorship and guidance with a team of leading experts in the fields of addiction, genetics, and
bioethics. The training and support provided by this award will facilitate the candidate’s long-term career goal as
an independent research scientist, building on her background in quantitative psychology, drug addiction, and
behavioral genetics. The proposed research, coupled with the candidate’s research potential, has the ability to
greatly expand the personal, clinical, and research utility of genomic prediction and to refine our understanding
of the genetic architecture of substance use.

## Key facts

- **NIH application ID:** 10908614
- **Project number:** 5K01DA057376-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Gretchen Saunders
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $160,119
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908614

## Citation

> US National Institutes of Health, RePORTER application 10908614, Improving cross ancestry polygenic prediction of tobacco and alcohol use (5K01DA057376-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10908614. Licensed CC0.

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