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Inter-generational Link of Cardio-Metabolic Risk: Integrate Multi-OMICs with Birth Cohort

Award Number: R01HD098232
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2024

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Inter-generational Link of Cardio-Metabolic Risk: Integrate Multi-OMICs with Birth Cohort - Abstract More than half of U.S. mothers entered pregnancy with overweight or obesity (OWO); maternal obesity is considered a major determinant of the next generations' OWO risk.7 A similar inter-generational link was observed for maternal hypertensive disorders before and during pregnancy. This inter-generational link may originate in utero and amplify the cardio- metabolic risk in current and future generations. However, questions remain about what the underlying mechanisms are and what can be done to mitigate the adverse effects of maternal cardio-metabolic disorders on offspring health. We propose to leverage the exceptional resources of the Boston Birth Cohort (BBC), one of the largest and longest U.S. high-risk urban low-income minority birth cohorts, to investigate the inter-generational link of cardio-metabolic outcomes and the role of maternal folate/B12 nutrition (modifiable early life factors), and to explore plausible epigenetic underpinnings. Furthermore, by combining fetal multi-omics data (genome, epigenome, and metabolome) with maternal and fetal epidemiological and clinical data, we seek to more precisely characterize newborns' future risk for the development of adverse cardio-metabolic outcomes up to age 21 years. Our proposal has a strong scientific premise. Both animal models and human studies implicate the intrauterine period as a critical time for the establishment of epigenetic variability. Epigenetic regulation has been implicated in a range of important biological functions, including adipogenesis, glucose homeostasis, inflammation, and insulin signaling. As such, fetal epigenetic mechanisms are critical for understanding an inter-generational link of cardio- metabolic disorders. However, currently there is no adequately powered prospective birth cohort study to assess the role of the fetal epigenome (using the latest profiling technology) along with maternal folate/B12 status in inter-generational cardio-metabolic risk in U.S. populations. Our proposal is also supported by promising preliminary data from the BBC, indicating that maternal folate status influences offspring DNA methylation and cardio-metabolic outcomes and mitigates the adverse effects of maternal cardio-metabolic disorders on offspring health. Successful completion of this study will improve our understanding of inter-generational cardio-metabolic risk and lead to a new paradigm for early prediction and prevention to halt or reverse the vicious inter-generational cycle, beginning at critical developmental windows when interventions may have the greatest impact on improving life-long health and reducing health disparities in current and future generations.


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 = $0 )
2024	2022	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	000	4	7/22/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $505,911 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	000	4	5/18/2022	NON-COMPETING CONTINUATION	$505,911
														Subtotal = $505,911

Issue Date FY: 2021 ( Subtotal = $762,473 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	000	3	6/24/2021	NON-COMPETING CONTINUATION	$762,473
														Subtotal = $762,473

Issue Date FY: 2020 ( Subtotal = $792,093 )
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	000	2	3/19/2020	NON-COMPETING CONTINUATION	$657,379
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	NIH Office of Research on Women's Health	001	2	7/13/2020	SUPPLEMENT FOR EXPANSION	$134,714
														Subtotal = $792,093

Issue Date FY: 2019 ( Subtotal = $674,709 )
2019	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	000	1	4/15/2019	NEW	$674,709
														Subtotal = $674,709

Grand Total All Awards = $2,735,186

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Inter-generational Link of Cardio-Metabolic Risk: Integrate Multi-OMICs with Birth Cohort

Award Number: R01HD098232

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/15/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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