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Genomic Characterization of Alzheimer Disease Risk in Admixed Populations with Native American and Southern European Genetic Ancestry

Award Number: R01AG070864
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Genomic Characterization of Alzheimer Disease Risk in Admixed Populations with Native American and Southern European Genetic Ancestry - ABSTRACT Alzheimer disease (AD) is the leading cause of dementia in older adults and occurs in all ethnic and racial groups. Genetic studies of AD have mostly been performed in non-Hispanic Whites (NHW) of Northern European (NE) ancestry. Only recently have efforts in AD started to expand into other populations, such as African-Americans (AA) and Hispanics (HI), and have a ready demonstrated differences in both risk effect size (e.g., APOE in AA and HI) and risk loci (e.g., ABCA7 in AA). Further evaluation demonstrates that genetic ancestry (as opposed to environmental/cultural factors) likely underlie at least part of this heterogeneity. Individuals with the Amerindian (AI) ancestry remain one of the most underrepresented groups in AD. Importantly, the NHW datasets did not differentiate among the Europeans (EU), whereas recent investigations showed that these pan-European results only partially overlap with the findings from populations from the Iberian Peninsula (IP) with Southern European (SE) ancestry. Caribbean and South American Hispanic populations are admixed with both AI and SE, thus making their study a critical scientific objective. Our proposed study enables testing the generalization of findings from NHW to these other ancestries, as well as identify AD risk/protective factors correlated specifically with AI and SE ancestry. Our results will allow for a better and more complete understanding of the genetic architecture of AD which will help improve disease prediction, prevention, diagnosis, and treatment in AI, admixed Hispanic populations, and beyond. To accomplish these goals, we propose three aims. In Aim 1 we will characterize known AD loci in admixed populations with AI and SE ancestry. This includes expanding collections, generalizing known AD loci to AI/SE populations, and variant discovery through admixture mapping and fine-mapping. In Aim 2 we will extend our Puerto Rican dataset by expanding PR multiplex families. This will allow more powerful linkage analyses, longitudinal neurocognitive and biomarker data, and the initiation of a brain donation program. Finally, in Aim 3 we will perform functional follow-up of variants using bioinformatics approaches, assessment of AD biomarkers, and assessment of cellular function using IPSc.


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 = $2,046,132 )
2025	2025	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Aging Research	000	5	3/4/2025	NON-COMPETING CONTINUATION	$2,046,132
														Subtotal = $2,046,132

Issue Date FY: 2024 ( Subtotal = $2,334,254 )
2024	2024	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Aging Research	001	4	7/1/2024	NON-COMPETING CONTINUATION	$233,425
2024	2024	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Aging Research	000	4	1/10/2024	NON-COMPETING CONTINUATION	$2,100,829
														Subtotal = $2,334,254

Issue Date FY: 2023 ( Subtotal = $2,266,674 )
2023	2023	UNIVERSITY OF MIAMI	1400 NW 10TH AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Aging Research	000	3	2/10/2023	NON-COMPETING CONTINUATION	$2,266,674
2023	2023	UNIVERSITY OF MIAMI	1400 NW 10TH AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Aging Research	001	3	6/6/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,266,674

Issue Date FY: 2022 ( Subtotal = $2,252,057 )
2022	2022	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Aging Research	000	2	4/28/2022	NON-COMPETING CONTINUATION	$2,252,057
														Subtotal = $2,252,057

Issue Date FY: 2021 ( Subtotal = $2,330,825 )
2021	2021	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Aging Research	000	1	1/27/2021	NEW	$2,330,825
														Subtotal = $2,330,825

Grand Total All Awards = $11,229,942

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Genomic Characterization of Alzheimer Disease Risk in Admixed Populations with Native American and Southern European Genetic Ancestry

Award Number: R01AG070864

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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