# Social, Genomic, and Epigenomic Drivers of Clopidogrel Response in Puerto Ricans

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $745,930

## Abstract

Project Summary
Pharmacogenomics has shown itself to be on the leading edge of clinical translatability in genomic medicine,
with findings that are currently implemented across the US and internationally. Clopidogrel is an oral prodrug
used to treat coronary artery disease. Several pharmacogenomic studies have consistently shown that single
nucleotide polymorphisms (SNPs) in CYP2C19 are associated with clopidogrel efficacy and adverse events. No
study has comprehensively studied the transcriptomic and epigenomic associations to clopidogrel response
outside of European populations, with no studies in admixed populations. Thus, the ability of non-European
populations to benefit equitably from those pharmacogenomic findings in clopidogrel is unknown. We propose a
study of clopidogrel response in admixed Caribbean Hispanics. Our preliminary data shows that local ancestry
is an important consideration in understanding genomic associations to clopidogrel response, gene expression
and predictive modeling in admixed populations. We have also included a study of SDoH within this study
population to assess how social factors may impact overall healthcare in this understudied population. We have
assembled a team with long-standing expertise in patient recruitment and engagement in Puerto Rico, public
health, pharmacogenomics, and genomic methods in admixed populations to accomplish 3 aims: AIM1: Creation
of a multi-omic dataset and predictors of clopidogrel response in PR. We will collect biospecimens for all 3 omics
data types (genomics, transcriptomics and epigenomics) in 200 participants at two time points (prior to
clopidogrel dosing and after 1 month of therapy), and from 200 healthy controls. We will measure P2Y12
Reactivity Units at each time point and will follow all participants for 1 year to identify adverse events. We will
compare differences in the transcriptome (platelet) and the DNA methylome for association to clopidogrel
response at each time point. AIM2: We will use both the Social Vulnerability Metric (SVM), a composite measure
of SDoH variables, and the CAT-SDoH, a computer adaptive personal assessment tool, to evaluate how social
vulnerability may impact the outcomes of clopidogrel drug therapy. AIM3: We will develop a platelet gene
expression prediction model using our LA-GEM methodology using healthy Caribbean Hispanic controls and
then conduct a TWAS on our Caribbean Hispanic clopidogrel cohort. Our proposed work will bring equity to the
pharmacogenomics of clopidogrel in this understudied population.

## Key facts

- **NIH application ID:** 10981740
- **Project number:** 1R01HG013773-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jorge Duconge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $745,930
- **Award type:** 1
- **Project period:** 2024-09-20 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981740

## Citation

> US National Institutes of Health, RePORTER application 10981740, Social, Genomic, and Epigenomic Drivers of Clopidogrel Response in Puerto Ricans (1R01HG013773-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10981740. Licensed CC0.

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