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Mosaic Loss of the Y Chromosome in Cardiac Amyloidosis

Award Number: R01AG086508
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Mosaic Loss of the Y Chromosome in Cardiac Amyloidosis - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $568,246 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	001	2	7/22/2025	NON-COMPETING CONTINUATION	$46,387
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	2	1/13/2025	NON-COMPETING CONTINUATION	$521,859
														Subtotal = $568,246

Issue Date FY: 2024 ( Subtotal = $599,966 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	1	4/3/2024	NEW	$599,966
														Subtotal = $599,966

Grand Total All Awards = $1,168,212

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Mosaic Loss of the Y Chromosome in Cardiac Amyloidosis

Award Number: R01AG086508

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/15/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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