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Common and Distinct Influences of Prenatal and Postnatal Early-Life Adversity on Epigenomic Trajectories in Mexican American Children

Award Number: R01MD016595
ORGANIZATION: NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Childhood obesity is a growing public health epidemic that is disproportionally affecting Hispanic children and associated with morbidity and downstream health disparities. Early-life adversity and childhood psychosocial stressors have been shown to contribute to obesity risk, with stronger effects reported among children growing up in lower-income households. The period of fetal development and early-life are marked by dynamic and rapid changes in fetal DNA methylation programming, epigenetic maturation of immune system-related genes in early- childhood and general physiological development. A poor and adverse social environment in early life has been hypothesized to contribute to epigenomic “weathering” leading to accelerated decline in health, aging and eventual health disparities, including obesity. A leading hypothesis for the origins of health disparities is the biological embedding of adversity on the epigenome due to chronic adversity exposure. While emerging evidence indicates that psychosocial stressors and adversity are associated with epigenetic biomarkers like DNA methylation, significant limitations remain in the field. Namely, most studies to date have been cross-sectional, used candidate gene approaches, not investigated changes or trajectories in epigenetic biomarkers throughout development, or functional consequences in gene expression. The proposed project will leverage data and samples from The Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a long- term study of low-income Latinx, predominantly Mexican American, mother-child pairs living in the Salinas Valley of California. We have repeated measurements and samples for DNA methylation analyses at birth, 7, 9, 14 and 18 years in approximately 300 mother-child pairs, genetics, and stabilized RNA for sequencing at 14 years of age. We will investigate both pre- and postnatal early-life adversity measures to 1) determine if adversity measures are associated with blood DNA methylation trajectories and subsequent variation in gene expression; 2) evaluate if adversity measures influence epigenetic aging clocks and biomarkers and their trajectories and if longitudinal changes are prospectively associated with obesity risk; and 3) determine if DNA methylation or epigenetic aging mediate associations with obesity and if an epigenetic adversity score can be constructed from children’s blood methylome. Our study will address critical gaps in the field by testing hypotheses prospectively over 18 years and addressing questions of persistence and embedment of pre- and postnatal adversity. We will test if epigenetic changes influence gene expression with untargeted RNA sequencing at 14 years. We will evaluate if DNA methylation can serve as a reliable biomarker of adversity in early-life and or alternatively if these biomarkers are causal for the relationship between adversity and obesity risk with mediation and mendelian randomization methods. Our approach will yield rigorous data to test the biological embedment of social adversity and its consequences in a Latinx, low-income birth cohort with high obesity prevalence.


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 = $568,642 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Minority Health and Health Disparities Research	001	3	2/25/2024	SUPPLEMENT FOR EXPANSION	$112,500
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Minority Health and Health Disparities Research	000	3	2/23/2024	NON-COMPETING CONTINUATION	$456,142
														Subtotal = $568,642

Issue Date FY: 2023 ( Subtotal = $670,535 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Minority Health and Health Disparities Research	000	2	3/11/2023	NON-COMPETING CONTINUATION	$593,606
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Minority Health and Health Disparities Research	001	2	9/1/2023	SUPPLEMENT FOR EXPANSION	$76,929
														Subtotal = $670,535

Issue Date FY: 2022 ( Subtotal = $617,675 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Minority Health and Health Disparities Research	001	1	7/20/2022	NEW	$0
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Minority Health and Health Disparities Research	000	1	7/13/2022	NEW	$617,675
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Minority Health and Health Disparities Research	002	1	8/15/2022	NEW	$0
														Subtotal = $617,675

Grand Total All Awards = $1,856,852

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Common and Distinct Influences of Prenatal and Postnatal Early-Life Adversity on Epigenomic Trajectories in Mexican American Children

Award Number: R01MD016595

ORGANIZATION: NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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