# Plasma proteomics in CHS and population biology

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $2,083,439

## Abstract

In studies of cardiovascular disease and aging, the emergence of various types of omics data has
transformed population science. In the last decade, for instance, genome-wide association studies (GWAS)
have identified and replicated thousands of genetic associations with measures of health and disease. Their
primary contribution has been an improvement in the understanding of the etiology of a variety of health
conditions—human population biology. These discovery efforts can lead rapidly to new therapies such as
the PCSK9 inhibitors. Likewise, proteomics can advance our understanding of biology. Proteins perform
most biological functions, and they are often not only the target of drug therapies, but also key biomarkers in
clinical medicine. Recent advances in technology have improved multiplexed protein assays and made
large scale studies in humans tractable.
 In the proposed project, we plan to assay 1310 plasma proteins in 3200 Cardiovascular Health Study
(CHS) participants with an aptamer-based method, one that has high sensitivity for low-abundance proteins
and high throughput for a large number of samples. A cohort study of older adults, CHS currently provides
active support, including central analysis, for eight phenotype-specific working groups (WGs). Each CHS
WG is led by one or two senior investigators and includes 10 to 20 junior or mid-career scientists. With
experience in genomics and a funded WG model, CHS is well-organized to take advantage of novel large-
scale phenotyping techniques such as proteomics to advance knowledge of human health and disease.
 The goal of the project is to use proteomics to improve our understanding of disease etiology and
prevention in older adults. The primary hypotheses involve an evaluation of associations between baseline
levels of circulating proteins and the incidence of a variety of health outcomes in prospective cohort
analyses in CHS. The plans are to release the protein-assay results immediately to the eight CHS WGs and
their 115 investigators, to provide central analytic support to the WGs, to offer mass-spectrometry-based
validation of selected proteins, and to leverage opportunities for replication in the Framingham Heart Study
and Jackson Heart Study. Multiple forms of genetic data, including whole-genome sequence data, are also
available to verify the identity of proteins and to establish their genetic determinants. In addition, Mendelian
randomization analyses will be used to examine supportive evidence for causal associations between
protein levels and health outcomes. For key proteins, new ELISA assays will be developed for additional
clinical research. The significance of this proposal lies in the combined strengths of the well-phenotyped
cohort of older adults, the rigorously validated proteomic technique, the available genetic data, the WG
structure, the central support for analysis, the assay validation efforts, the replication plans, the productive
CHS WG members, and the data-shari...

## Key facts

- **NIH application ID:** 9976578
- **Project number:** 5R01HL144483-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** ROBERT E GERSZTEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,083,439
- **Award type:** 5
- **Project period:** 2019-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976578

## Citation

> US National Institutes of Health, RePORTER application 9976578, Plasma proteomics in CHS and population biology (5R01HL144483-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976578. Licensed CC0.

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