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Whole Genome Sequencing and Admixture Analyses of Neuropathologic Traits in Diverse Cohorts in USA and Brazil

Award Number: R01AG075927
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Whole Genome Sequencing and Admixture Analyses of Neuropathologic Traits in Diverse Cohorts in USA and Brazil - Identifying molecular drivers of Alzheimer’s disease and related dementias (AD/ADRD) pathologies is an urgent public health priority. This is especially important in persons of African Ancestry. The overall goal of the proposed study is to identify genes and proteins that drive common AD/ADRD pathologic traits. We previously used multi-level omics to identify molecular drivers of AD/ADRD pathologic traits in non-Latino whites. The proposed study, submitted in response to NOT-AG-18-053 will extend this work by leveraging an unique, ongoing, diverse study being conducted in Sao Paulo, Brazil, called “Pathology, Alzheimer´s and Related Dementias Study” (PARDoS) and five other diverse cohorts in the USA, with whole genome sequencing (WGS) on more than 1350 diverse autopsied participants. PARDoS is prospectively generating neuropathologic and clinical AD/ADRD traits, and DNA on admixed Brazilians of European and African, and to a lesser extent Native Brazilian ancestry. The proposal has the following Aims. Aim 1 will generate WGS on an additional 7650 persons in collaboration with the Alzheimer’s Disease Sequencing Project (ADSP). Aim 2 will perform deep admixture mapping of known SNPs for Alzheimer’s dementia, to determine their associations with AD/ADRD neuropathologic phenotypes in 6500 admixed Brazilian brains followed generalization to 300 diverse brains from the USA, and discovery analyses for 5500 Brazilians followed by generalization to 2000 diverse samples in the USA. Aim 3 will computationally determine telomere length (TL) and examine their association with AD/ADRD clinical and pathologic traits. An exploratory analysis will examine for rare variant associations with AD/ADRD neuropathologic traits. Aim 5 will examine the association of mitochondrial DNA to AD/ADRD traits.


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 = $0 )
2026	2025	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	001	3	4/17/2026	SUPPLEMENT FOR EXPANSION	$0
2026	2025	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	3	4/17/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $3,930,984 )
2025	2025	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	3	9/12/2025	NON-COMPETING CONTINUATION	$3,251,970
2025	2025	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	001	3	9/17/2025	SUPPLEMENT FOR EXPANSION	$679,014
														Subtotal = $3,930,984

Issue Date FY: 2024 ( Subtotal = $3,731,942 )
2024	2024	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	001	2	9/20/2024	NON-COMPETING CONTINUATION	$0
2024	2024	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	2	8/30/2024	NON-COMPETING CONTINUATION	$3,731,942
														Subtotal = $3,731,942

Issue Date FY: 2023 ( Subtotal = $3,671,787 )
2023	2023	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	1	8/8/2023	NEW	$3,671,787
														Subtotal = $3,671,787

Grand Total All Awards = $11,334,713

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Whole Genome Sequencing and Admixture Analyses of Neuropathologic Traits in Diverse Cohorts in USA and Brazil

Award Number: R01AG075927

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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