# Mosaic Loss of the Y Chromosome in Cardiac Amyloidosis

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $599,966

## Abstract

SUMMARY/ABSTRACT
Transthyretin cardiac amyloidosis (ATTR) is a prevalent, yet underappreciated and underdiagnosed condition
that gives rise to a particularly lethal form of heart failure with preserved ejection fraction (HFpEF). An unusual
aspect of ATTR is its strong male bias (94% male in wild-type ATTR and 72% in mutant ATTR). We hypothesize
that the mosaic loss of the Y chromosome (mLOY) in the hematopoietic system plays a role in the etiology of
ATTR. mLOY is the most prevalent postzygotic mutation in males. mLOY describes the clonal loss of the Y
chromosome in cells that frequently arises in the hematopoietic system. Recent work by the Walsh lab has
associated mLOY with incident cardiovascular disease in humans and demonstrated that experimental LOY in
the hematopoietic system can lead to spontaneous heart failure in mice (Sano et al. Science 2022). More
recently, we have found association between mLOY and TTR cardiac amyloidosis in the patient population,
providing a compelling rationale for the strong sex bias that is common to this condition. Thus, the causal and
mechanistic relationships between mLOY and cardiac amyloidosis will be explored.

## Key facts

- **NIH application ID:** 10859503
- **Project number:** 1R01AG086508-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** KENNETH WALSH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $599,966
- **Award type:** 1
- **Project period:** 2024-04-15 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10859503

## Citation

> US National Institutes of Health, RePORTER application 10859503, Mosaic Loss of the Y Chromosome in Cardiac Amyloidosis (1R01AG086508-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10859503. Licensed CC0.

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