# Ancestry and sex-related pharmacogenomic and metabolomic signatures of oral anticoagulant response

> **NIH NIH K23** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $169,222

## Abstract

Oral anticoagulants (OACs), including warfarin and direct oral anticoagulants (DOACs), form the cornerstone
of therapy for thromboembolic conditions. However, individual variability in OAC response can result in lack of
efficacy (thromboembolism) or safety (hemorrhage), with OAC-related hemorrhage a serious adverse effect.
Ancestry and sex influence OAC response and variable drug levels, therapeutic target levels, and clinical OAC
responses have been observed. Differences in pharmacogenomic variant frequencies, gene expression, and
metabolite profiles by ancestry and sex may explain variable drug response. However, pharmacogenomic
evaluations of DOAC response have been limited in diversity, evaluated candidate genes, and lacked
evaluation of sex-related predictors. Furthermore, metabolomics signatures of variable OAC response have not
been evaluated. This is a major barrier to establishing therapeutic drug and biomarker levels and personalizing
OAC therapy. The NIH recognizes the importance of identifying factors that affect treatment response among
diverse patients and the use of pharmacogenomics and metabolomics to identify and develop new therapeutic
targets/ biomarkers. With the support of this K23 award, Brittney Davis, PharmD will identify and evaluate
ancestry and sex-related pharmacogenomic and metabolomic signatures of variable OAC response, including
pharmacokinetics (PK), pharmacodynamics (PD), and clinical outcomes (hemorrhage). This will be achieved
through integrated research and training aims that build on her prior clinical and research background.
Specifically, she will evaluate pharmacogenomic predictors of DOAC PK (drug levels) and PD (anti-Xa levels),
and integrate pathway and functional effects to characterize drug response pathways (Aim 1). To evaluate
clinical outcomes, she will identify pharmacogenomic predictors of OAC-related hemorrhage employing a
DOAC-specific approach and a combined drug class approach (warfarin + DOAC), and replicate findings in an
independent cohort identified using electronic medical record (EMR)-based phenotyping (Aim 2). Finally, she
will conduct metabolomics analysis and characterize signatures of anti-Xa and OAC-related hemorrhage to
determine if metabolite profiles can be serve as OAC response biomarkers. This project provides a highly
significant opportunity to employ strategies to identify and target DOAC and anti-Xa threshold concentrations,
which could help maximize efficacy and safety, elucidate biologic pathways and metabolomic signatures of
variable response, and lay the foundation for personalized strategies. To achieve her research and career
goals, Dr. Davis has constructed a multidisciplinary mentoring team with extensive expertise in areas relevant
to her career development, including 1) bioinformatics/statistical genetics 2) metabolomics and pathway
analysis 3) electronic medical record (EMR)-based phenotyping and 4) clinical research. This mentored
training experience at the Univ...

## Key facts

- **NIH application ID:** 10886294
- **Project number:** 1K23HL165031-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Brittney H Davis
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $169,222
- **Award type:** 1
- **Project period:** 2024-09-18 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886294

## Citation

> US National Institutes of Health, RePORTER application 10886294, Ancestry and sex-related pharmacogenomic and metabolomic signatures of oral anticoagulant response (1K23HL165031-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10886294. Licensed CC0.

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