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Identifying genetically driven gene dysregulation in Alzheimer's disease and related dementias using statistical data integration

Award Number: R01AG078657
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Identifying genetically driven gene dysregulation in Alzheimer's disease and related dementias using statistical data integration - PROJECT SUMMARY Alzheimer’s disease (AD) and related dementias (ADRD) are highly heritable, severe, and complex brain disorders. Molecular profiling efforts of the brain have enabled us to understand more about how common variants may be associated with disease risk via regulating gene expression. However, the status quo as it pertains to the use of multiomics data for gene-trait association, is limited to independent transcriptome- and proteome-wide association studies. Here, we propose to: (1) additionally leverage epigenetic datasets and (2) apply a data-driven correlation-aware meta-analytic approach to integrate a wide range of brain cell-type and area specific imputed transcriptomes, proteomes and epigenomes. Our preliminary data suggest that this will greatly increase the power to identify genetically driven gene dysregulation associated with these disorders while controlling for the correlation between different genomic features. First, we will impute brain cell-type (based on FANS/FACS-sorted and single-nucleus data) and brain area (PFC, ACC, EC, STG, IFG) specific transcriptomes, proteomes and epigenomes for AD, frontotemporal lobar degeneration, and dementia with Lewy bodies. Secondly, for each disease, we will perform a data-driven correlation-aware meta-analysis of these imputed genomic features to identify key genes. Lastly, we will develop an open resource that provides for the rapid dissemination and open access to analyses and outcomes. To our knowledge, the proposed approach will result in the largest multiscale modeling of genetically driven gene dysregulation in the brain, will identify novel genes associated with dementias and will enable similar studies in other brain disorders as well.


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: 2026 ( Subtotal = $670,825 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	001	4	2/23/2026	NON-COMPETING CONTINUATION	$67,083
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	4	12/23/2025	NON-COMPETING CONTINUATION	$603,742
														Subtotal = $670,825

Issue Date FY: 2025 ( Subtotal = $657,408 )
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	3	12/5/2024	NON-COMPETING CONTINUATION	$603,742
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	001	3	9/23/2025	NON-COMPETING CONTINUATION	$53,666
														Subtotal = $657,408

Issue Date FY: 2024 ( Subtotal = $670,825 )
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	001	2	5/17/2024	NON-COMPETING CONTINUATION	$67,083
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	2	12/14/2023	NON-COMPETING CONTINUATION	$603,742
														Subtotal = $670,825

Issue Date FY: 2023 ( Subtotal = $670,825 )
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	1	3/30/2023	NEW	$670,825
														Subtotal = $670,825

Grand Total All Awards = $2,669,883

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Identifying genetically driven gene dysregulation in Alzheimer's disease and related dementias using statistical data integration

Award Number: R01AG078657

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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