# Genetic and social determinants of pharmacological health outcomes in ancestrally diverse populations (Warren)

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $72,540

## Abstract

PROJECT SUMMARY/ABSTRACT
Pharmacogenomics has the potential to dramatically improve health care outcomes, but is currently failing on
diversity among its research participants. As a consequence, we do not fully understand all of the factors
influencing pharmacological response in underrepresented populations, including those that contribute to
racial/ethnic differences in drug efficacy and safety as reported by Food and Drug Administration (FDA) drug
labels. For example, the clinical validity of genetic variants that are common in research participants from
historically-excluded populations (e.g., lower proportions of European genetic ancestry) but rare in well-
represented study populations remains unknown. In addition, gene expression studies have already provided
insight into the underlying biology of disease susceptibility for numerous conditions beyond what genome wide
association study (GWAS) results alone have discovered, but have not been fully applied to studies of
pharmacogenomic discovery. Furthermore, social determinants of health may impact pharmacological drug
response from a biological standpoint even after taking into account the effects of these factors on drug
adherence, access, and utilization (e.g. social determinants of epigenetics). Addressing this gap in knowledge
has the potential to prevent future healthcare disparities that may be exacerbated as the infrastructure to support
clinical pharmacogenomics continues to gain traction across health institutions nationwide. Furthermore,
elucidation of the genetic and nongenetic contributors to differences in drug response across race/ethnicity will
obviate the use of this population descriptor as a proxy for these factors. Pharmacogenomic studies using large,
diverse datasets are necessary to ensure that advances in this field benefit individuals equitably.
Our primary goal in this project is to identify genetic and social determinants of pharmacological drug response
among racial/ethnic minorities. To accomplish this goal, we will leverage data from the Kaiser Permanente
Research Biobank (KPRB) and the National Institutes of Health (NIH) All Of Us research program, which are two
of the largest electronic health record-linked biobanks in the United States. These cohorts are ideal for the
proposed studies because they are large (>400,000 participants each), diverse (>25% racial/ethnic minorities),
linked to genome-wide genetic data, and capture social determinants of health.
In Aim 1, we will evaluate the relative contribution of genetic ancestry versus social factors on race/ethnicity-
based differences in drug efficacy and safety. In Aim 2, we will identify genome-wide polymorphisms predictive
of drug effects in historically-excluded populations from large pharmacogenetics studies. In Aim 3, we will use
ancestry-specific gene expression results to identify genetic determinants of drug response. The aims will be
carried out by an established multidisciplinary team of experts in c...

## Key facts

- **NIH application ID:** 11089053
- **Project number:** 3R01HG012824-02S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Akinyemi Oni-Orisan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $72,540
- **Award type:** 3
- **Project period:** 2024-09-18 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11089053

## Citation

> US National Institutes of Health, RePORTER application 11089053, Genetic and social determinants of pharmacological health outcomes in ancestrally diverse populations (Warren) (3R01HG012824-02S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11089053. Licensed CC0.

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