# Genetic Determinants of Lipidomic Variation and Their Role in CVD Risk

> **NIH NIH R01** · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · 2020 · $616,156

## Abstract

PROJECT SUMMARY
Cardiovascular disease (CVD) is a heterogeneous disease encompassing a broad range of heart and
vasculature disorders and is the number one cause of death worldwide. A well-established relationship exists
between quantitative variation in the plasma lipid levels and CVD risk; however, the exact mechanism is unclear.
Lipids play a crucial role in cell, tissue and organ physiology, and their metabolism is tightly regulated; however,
in many human diseases lipid metabolism is disrupted. The classical lipid parameters (HDL-C, LDL-C, and
triglycerides) most commonly examined in relation to disease risk are themselves complex entities composed of
multiple lipid species. We hypothesize that these basic lipid species represent unique phenotypes that are better
predictors of disease risk and may lead to the more rapid discovery of genes causally involved in lipid variation
and cardiovascular disease.
In this project we will exploit whole genome sequence (WGS) information using a mixed longitudinal design in
powerful extended pedigrees of Mexican American individuals in combination with comprehensive measures of
the human lipidome, to identify novel genes and functional variants influencing lipid variation and risk of CVD
development. This project will generate novel lipid endophenotypes that may represent better predictors of
disease risk. The combination of these precise biological phenotypes and WGS gives us an unprecedented
opportunity to identify novel genes and functional variants influencing human lipid variation and risk of CVD. To
achieve these objectives, we will (I) perform untargeted lipid profiling in 500 Mexican American individuals from
seven large SAFS pedigrees, identify those species genetically correlated with CVD-related traits and
incorporate these into a targeted assay to profile in all individuals; (II) perform targeted lipid profiling in 2,500
Mexican American individuals followed by quantitative genetic analyses; (III) identify novel sequence variation
influencing lipid variation and CVD risk in all individuals using WGS; (IV) perform replication in an independent
Mexican American population, the Cameron County Hispanic Cohort.
CVD is the leading cause of death globally, posing a huge economic burden. The ability to identify genes that
are causally involved in disease risk provides an unparalleled opportunity to quickly determine biological
pathways that are involved in disease pathology. A better understanding of the genetic contribution to lipid
variation and CVD development will provide novel approaches for the characterization, treatment and potential
prevention of this costly disease.

## Key facts

- **NIH application ID:** 9841984
- **Project number:** 5R01HL140681-03
- **Recipient organization:** UNIVERSITY OF TEXAS RIO GRANDE VALLEY
- **Principal Investigator:** JOANNE E. CURRAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $616,156
- **Award type:** 5
- **Project period:** 2018-01-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841984

## Citation

> US National Institutes of Health, RePORTER application 9841984, Genetic Determinants of Lipidomic Variation and Their Role in CVD Risk (5R01HL140681-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9841984. Licensed CC0.

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