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Host genetics, early-life microbiome, and childhood asthma: MARC-43 Boston

Award Number: UH3OD023253
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/21/2016
PERIOD OF PERFORMANCE END DATE: 05/31/2030

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Host genetics, early-life microbiome, and childhood asthma: MARC-43 Boston - Recent studies report probabilistic associations between the early-life microbiome and various child health outcomes (e.g., obesity, asthma), suggesting potential insights into pathogenesis and subsequent, targeted development of preventive interventions. However, the causal role of the early-life microbiome on child health remains unclear. Our preliminary work has applied state-of-art statistical genetics and causal inference approaches to large genetics and microbiome data in our ECHO-supported cohorts, demonstrating: 1) host genetic loci for airway Streptococcus across different populations, 2) host genetic loci for gut microbiome and significantly enriched biological pathways (e.g., regulation of neuron development, glucuronate interconversions), and 3) relationship of gut Bacteroides with obesity and asthma risk. Our central hypothesis is that the genetically driven gut and upper airway microbiome in the first two years of life has a causal role in the development of child health outcomes, such as obesity and airway outcomes. This UG3/UH3 project will test this innovative hypothesis by applying the latest statistical genetics and epidemiological methods—e.g., microbiome genome-wide association study (mGWAS)— to large ECHO genetics, microbiome, and extensive clinical and environmental data. By using ECHO core data elements, Aim 1 will generate mGWAS summary statistics to enable researchers to examine the causal role of the early-life microbiome on child health outcomes. For example, by using the mGWAS and Mendelian randomization approaches, we will determine the causal role of the gut and nasal airway microbiome (during age 0-1.9 years) in the risk of developing childhood obesity. By using specialized airway outcome data, Aim 2 will determine whether the genetically driven gut and nasal microbiome has a causal effect on the development of asthma (and its major phenotypes) and on lower lung function in later childhood. Aim 3 will maximize the retention of existing ECHO Cohort Protocol (ECP) participants and implement the ECP with high fidelity. (To date, in MARC-43 Boston participants, ECP retention is 100%, with >80% data completeness.) The proposed project will serve as a national research resource for examining the causal role of early-life microbiome in various childhood health outcomes. Furthermore, the project will provide a robust evidence base for the future development of targeted microbiome interventions to prevent childhood obesity and asthma. The investigators are NIH-funded researchers with international expertise in all relevant fields (e.g., epidemiology, statistical genetics, microbiome, childhood obesity, asthma). The project matches well with the goals of the ECHO Program.


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 = $737,243 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Trans-NIH Research Support	000	10	6/10/2025	EXTENSION WITH OR WITHOUT FUNDS	$737,243
														Subtotal = $737,243

Issue Date FY: 2024 ( Subtotal = -$459 )
2024	2022	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Trans-NIH Research Support	000	7	4/2/2024	NON-COMPETING CONTINUATION	-$459
														Subtotal = -$459

Issue Date FY: 2022 ( Subtotal = $2,259,392 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Trans-NIH Research Support	001	7	8/19/2022	NON-COMPETING CONTINUATION	$2,259,392
2022	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Trans-NIH Research Support	000	6	5/26/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,259,392

Issue Date FY: 2021 ( Subtotal = $225,863 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Trans-NIH Research Support	001	6	8/25/2021	NON-COMPETING CONTINUATION	$225,863
2021	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Trans-NIH Research Support	000	5	8/4/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $225,863

Issue Date FY: 2020 ( Subtotal = $1,368,451 )
2020	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Trans-NIH Research Support	000	5	8/19/2020	NON-COMPETING CONTINUATION	$1,368,451
														Subtotal = $1,368,451

Issue Date FY: 2019 ( Subtotal = $4,808,859 )
2019	2019	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Trans-NIH Research Support	003	4	9/6/2019	NON-COMPETING CONTINUATION	$3,578,504
2019	2018	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Trans-NIH Research Support	000	3	10/26/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
2019	2018	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Trans-NIH Research Support	002	3	6/24/2019	EXTENSION WITH OR WITHOUT FUNDS	-$230,257
2019	2018	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Trans-NIH Research Support	001	3	2/5/2019	EXTENSION WITH OR WITHOUT FUNDS	$1,460,612
														Subtotal = $4,808,859

Issue Date FY: 2018 ( Subtotal = $3,227,769 )
2018	2018	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Trans-NIH Research Support	000	3	8/29/2018	EXTENSION WITH OR WITHOUT FUNDS	$3,227,769
														Subtotal = $3,227,769

Grand Total All Awards = $12,627,118

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Host genetics, early-life microbiome, and childhood asthma: MARC-43 Boston

Award Number: UH3OD023253

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/21/2016

PERIOD OF PERFORMANCE END DATE: 05/31/2030

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