# Pharmacogenomic effects of scavenger B1 in cardiovascular disease prevention

> **NIH NIH R03** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $89,500

## Abstract

PROJECT SUMMARY/ ABSTRACT
 Despite mixed evidence of efficacy, drugs like aspirin, and vitamin supplements, are widely used in the
US population to prevent chronic diseases. The failure of randomized trials of these over-the-counter (OTC)
drugs to consistently demonstrate efficacy, may in part be attributed to a complex interacting heterogeneity of
genetic and other effects. Identifying pharmacogenomically defined subpopulations for benefit or harm from
drugs and supplements, could enhance precision prevention of cardiovascular disease (CVD), one of the
leading causes of death worldwide. Thus, pharmacogenomics, the study of how genomic variation modifies
effects of pharmacologically active compounds, has the potential to guide development of precision CVD
prevention strategies. Our group has identified candidate genes from multiple pathways related to
cardiovascular function that modify the effects of aspirin, and vitamin E in randomized CVD prevention trials.
Preliminary data from the Women’ Health Study (WHS), suggests that SCARB1, the gene encoding scavenger
B1, a major HDL receptor, is a novel candidate gene for both aspirin and vitamin E effect modification in CVD
prevention. Translation of pharmacogenomic markers requires identification of the full set of actionable
pharmacogenomic targets, elucidation of their underlying mechanism, and replication of their effects in other
cohorts. In this proposal, we examine SCARB1 pharmacogenomic effects on CVD in the WHS and four
validation cohorts, ASPirin in Reducing Events in the Elderly (ASPREE), The Physician’s Health Study (PHS),
The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC), and The Partner’s Biobank (PBB),
allowing broad generalizability of these findings.
 Given the complexity of CVD and the number of pathways highlighted by pharmacogenomic candidate
genes, – estrogen and catecholamine metabolism (COMT), nitric oxide signaling (GUCY1A3), and cholesterol
transport (LPA and SCARB1), – there are likely many more pharmacogenomic loci that give rise to a
heterogeneity of effects. Identification of the full complement of treatment modifying genes is required to define
effects of these overlapping pathways on efficacy and safety of CVD preventive therapy. Currently, discovery
of pharmacogenomic loci is limited to candidate gene analysis because genome-wide association study
(GWAS) datasets from clinical trials lack sufficient disease events to power classical statistical models.
Machine learning approaches, like random forests (RF) obviate the need for statistical power offering an
alternative path to discovery. Here, we propose to identify and validate combinatorial pharmacogenomic effects
that influence aspirin and vitamin E in CVD prevention in The WHS and PBB by using the RF machine learning
methodology. Thus, this proposal seeks to accelerate translation of precision cardiovascular disease
prevention by identifying and validating individual and combinatorial effects of novel...

## Key facts

- **NIH application ID:** 10347622
- **Project number:** 1R03HL157890-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Kathryn Tayo Hall
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $89,500
- **Award type:** 1
- **Project period:** 2022-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10347622

## Citation

> US National Institutes of Health, RePORTER application 10347622, Pharmacogenomic effects of scavenger B1 in cardiovascular disease prevention (1R03HL157890-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10347622. Licensed CC0.

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