# Uncovering early signals of hereditary TTR amyloidosis in minority populations at high genetic risk

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $564,275

## Abstract

PROJECT SUMMARY
The odyssey to a diagnosis for patients with hereditary TTR amyloidosis (hATTR) often lasts years because the
signs and symptoms are non-specific. Meanwhile, patients can progress to advanced heart disease (cardiac
amyloidosis) and nerve disease (polyneuropathy). A common pathogenic TTR variant impacting African
American (4%) and Hispanic/Latino (1%) patients, V142I, confers particularly high risk for cardiac amyloidosis,
but diagnostic delays keep these groups at the margins of care. Novel therapies are now available to delay
hATTR progression; however, they cannot reverse the disease. For this reason, it is imperative to diagnose
hATTR at the earliest possible stages, when these therapies are likely to be most beneficial. Because the gold
standard for non-invasive diagnosis of hATTR-related cardiac amyloidosis, nuclear scintigraphy, involves
exposure to ionizing radiation and the sensitivity in asymptomatic patients is unknown, widespread screening by
this method is not yet justified. Traditional phenotype-first studies have identified non-cardiac red flag signs and
symptoms that herald future heart disease, but the complete phenotypic spectrum and natural history of hATTR
are not well understood, particularly in individuals at high genetic risk. To date, large diverse cohorts of individuals
with pathogenic TTR variants (TTR+) have not been extensively studied to understand the full range of clinical
features of hATTR. We propose a genotype-first study of predominantly African American and Hispanic/Latino
TTR+ individuals from the electronic health record (EHR)-linked BioMe Biobank in New York City. First, we will
perform retrospective deep phenotyping using EHRs to characterize the scope and develop a timeline of cardiac
and non-cardiac features of hATTR, and estimate age-dependent penetrance. We will perform a well-powered
phenome-wide association study, in collaboration with other biobanks, to identify novel health traits associated
with V142I. Clinical characteristics found to be enriched in TTR+ individuals will be accrued into a phenotype risk
score to help identify patients at risk for hATTR in health systems. In addition, we will conduct a prospective
study to generate evidence informing guidelines for optimal mode and timing of cardiac imaging surveillance in
high-risk TTR+ individuals across adulthood. We will recruit 100 TTR+ individuals from BioMe into a multimodal
cardiac imaging study using gold standard and cutting-edge experimental imaging approaches. Through these
endeavors, we will delineate a timeline of anticipatory systemic and cardiac imaging signatures unique to
individuals at high genetic risk for hATTR. The results will empower clinicians to recognize the disease at its
earliest stages so patients may maximally benefit from therapy. We posit that although hATTR is currently grossly
underdiagnosed in U.S. minority patients, it is in fact amenable to earlier detection through discovery of prescient
signs a...

## Key facts

- **NIH application ID:** 10100303
- **Project number:** 1R01HL155356-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** NOURA SERENE ABUL-HUSN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $564,275
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10100303

## Citation

> US National Institutes of Health, RePORTER application 10100303, Uncovering early signals of hereditary TTR amyloidosis in minority populations at high genetic risk (1R01HL155356-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10100303. Licensed CC0.

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