# Identifying Proteomics Risk Markers for Abdominal Aortic Aneurysm

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $814,292

## Abstract

Project Summary
Abdominal aortic aneurysm (AAA) is an important cause of morbidity and mortality in older adults. AAA rupture
carries a ≥ 65% mortality rate. There are no direct pharmaceutical treatments for AAA, so the main
management options are screening, secondary risk factor intervention, and surgical repair for large AAAs,
which carries risk. Our previously funded AAA R01 “Identifying Epidemiological Risk Factors for Abdominal
Aortic Aneurysm” established one of the few large population-based prospective US cohorts to identify
etiologic risk factors for incident AAA. Among 15,792 ARIC participants followed for more than two decades,
we ascertained 665 AAAs, identified novel middle-age risk markers for AAA, and estimated the lifetime risk for
AAA from age 45 to be 5.6%. Building upon our original R01 and an ongoing proteomic project in ARIC, we
propose a 4-year study to identify proteomics risk markers and investigate novel mechanisms and etiological
pathways for AAA. Our specific aims are to: (1) Leverage a large panel of aptamer-based, plasma proteomics
data (n=4,931 human proteins) in the entire ARIC cohort from Visits 2 and 3, to conduct a prospective study of
proteomic risk markers for AAA (n=552 cases) over 24 years of follow-up, and to replicate significant proteins
identified in nested AAA case (n=518)-cohort (n=833) samples from the prospective, population-based HUNT3
and SCCS studies. We will use a combination of targeted and agnostic approaches. To ensure the accuracy
and generalizability of our findings, we will also identify commercial assays or develop targeted quantitative
liquid chromatography-mass spectrometry assays for the top 5 novel, replicated, aptameric-based proteins and
then compare the targeted protein levels with the aptamer-based measurements in 200 ARIC plasma samples.
(2) Conduct genome-wide association study (GWAS) in ARIC for proteins identified and replicated in Aim 1,
and replicate any significant genetic associations in HUNT3 (n=4,230), MESA (n=5,351), and published protein
GWAS database. We will also conduct a Mendelian randomization study, incorporating data from the
international AAA GWAS Consortium (10,204 AAAs and 107,766 controls), to elucidate the causal relation
between significant protein biomarkers and AAA, followed by a network analysis to integrate the genomic and
proteomic findings.
This study will use unsurpassed proteomic resource in ARIC and other cohorts to identify new risk factors and
mediators of AAA, with potential implications for AAA prevention and treatment.

## Key facts

- **NIH application ID:** 10295903
- **Project number:** 1R01HL155209-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Weihong Tang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $814,292
- **Award type:** 1
- **Project period:** 2021-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10295903

## Citation

> US National Institutes of Health, RePORTER application 10295903, Identifying Proteomics Risk Markers for Abdominal Aortic Aneurysm (1R01HL155209-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10295903. Licensed CC0.

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