Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Alzheimer Disease Genetic Architecture in African Americans

Award Number: R01AG048927
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2015
PERIOD OF PERFORMANCE END DATE: 04/30/2026

Group Awards By:

View Award Description

Alzheimer Disease Genetic Architecture in African Americans - ABSTRACT A portion of the genetic component of Alzheimer disease (AD) is explained by genes identified by positional cloning, targeted gene analysis, GWAS and next generation sequencing approaches. With few notable exceptions, the functional variants in these genes and precise pathogenic mechanisms by which these variants lead to AD are unknown. We will continue to direct our efforts on persons of African ancestry (AA), a group with a high incidence of dementia but studied much less than persons of European ancestry (EA). We will leverage rich AD-related endophenotype and other risk factor data from the largest collection of AAs assembled by us, the Alzheimer Disease Genetics Consortium (ADGC) and Alzheimer Disease Sequencing Project (ADSP) for genetic studies of AD to promote further discovery of AD-related genes and variants as well as their mechanisms of action leading to AD. Previously, we demonstrated significant association of AD with SORL1, AKAP9, and other genes in AAs using standard and novel analytic approaches. In the next project period, we will perform RNA sequencing on brain tissue obtained from more than 140 AA AD cases and controls, and analyze these data using state-of-the-art bioinformatics approaches to assess the influence of AD risk variants on gene expression. We will construct AA-specific Bayesian elastic-net models of genetically- mediated gene expression using the AA brain cohort genotype and RNAseq data. These models will be applied to AA cohorts from the ADGC and ADSP (total n=9,200) using PrediXcan to construct AA-specific expression predictions In addition, we will identify non-genetic mediators of genetic influences on AD risk by (1) performing gene ˣ environment GWASs of AD in AAs using data for several established AD risk factors using data from the ADGC/ADSP, UK Biobank and Million Veterans Program; (2) applying mendelian randomization to assess the causal relationship between diabetes, cigarette smoking, hypertension, hypercholesterolemia, obesity and AD in AAs using existing GWAS summary statistics for these traits in AAs; and (3) conducting a phenome-wide association study (PheWAS) to identify pleiotropy by deriving a polygenic risk score for AD in AAs and testing its association with a range of phenotypes within the UK Biobank. We will also perform in vitro experiments (including knockdown by siRNA, gene and protein over-expression, immunofluorescence, and ELISA) in human neuronal cells and induced pluripotent stem cell-derived neurons containing AA AD risk variants inserted by CRISPR to understand how genetic variation in AKAP9 and other promising genes leads to AD-related pathologic states as well as to provide models that can be used in small molecule drug screens for potential AD treatments.


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: 2024 ( Subtotal = $687,987 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	10	4/15/2024	NON-COMPETING CONTINUATION	$687,987
														Subtotal = $687,987

Issue Date FY: 2023 ( Subtotal = $687,987 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	9	5/2/2023	NON-COMPETING CONTINUATION	$687,987
														Subtotal = $687,987

Issue Date FY: 2022 ( Subtotal = $775,159 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	8	5/18/2022	NON-COMPETING CONTINUATION	$775,159
														Subtotal = $775,159

Issue Date FY: 2021 ( Subtotal = $1,189,947 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	002	7	6/16/2021	NON-COMPETING CONTINUATION	$775,571
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	003	7	8/24/2021	SUPPLEMENT FOR EXPANSION	$414,376
2021	2020	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	001	6	2/2/2021	COMPETING CONTINUATION	$259,459
2021	2019	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	5	2/2/2021	NON-COMPETING CONTINUATION	-$259,459
														Subtotal = $1,189,947

Issue Date FY: 2020 ( Subtotal = $813,421 )
2020	2020	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	001	6	5/6/2020	COMPETING CONTINUATION	$813,421
2020	2019	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	5	4/27/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $813,421

Issue Date FY: 2019 ( Subtotal = $537,696 )
2019	2019	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	5	1/28/2019	NON-COMPETING CONTINUATION	$537,696
														Subtotal = $537,696

Issue Date FY: 2018 ( Subtotal = $951,144 )
2018	2018	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	003	4	8/6/2018	SUPPLEMENT FOR EXPANSION	$347,662
2018	2018	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	002	4	6/26/2018	NON-COMPETING CONTINUATION	$0
2018	2018	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	4	1/22/2018	NON-COMPETING CONTINUATION	$543,134
2018	2018	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	001	4	4/19/2018	NON-COMPETING CONTINUATION	$60,348
														Subtotal = $951,144

Issue Date FY: 2017 ( Subtotal = $643,341 )
2017	2017	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	001	3	6/21/2017	NON-COMPETING CONTINUATION	$64,333
2017	2017	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	3	12/23/2016	NON-COMPETING CONTINUATION	$579,008
														Subtotal = $643,341

Issue Date FY: 2016 ( Subtotal = $813,495 )
2016	2016	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	001	2	4/26/2016	SUPPLEMENT FOR EXPANSION	$164,366
2016	2016	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	000	2	1/30/2016	NON-COMPETING CONTINUATION	$649,129
														Subtotal = $813,495

Issue Date FY: 2015 ( Subtotal = $652,832 )
2015	2015	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	000	1	2/5/2015	NEW	$652,832
														Subtotal = $652,832

Grand Total All Awards = $7,753,009

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Alzheimer Disease Genetic Architecture in African Americans

Award Number: R01AG048927

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/15/2015

PERIOD OF PERFORMANCE END DATE: 04/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer