Thursday, July 3, 2025 7/3/2025

Genetic and Epigenetic Effects on Childhood Cognitive Trajectories

Award Number: R01NR019245
ORGANIZATION: NATIONAL INSTITUTE OF NURSING RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2025

Group Awards By:

View Award Description

Genetic and Epigenetic Effects on Childhood Cognitive Trajectories - PROJECT SUMMARY/ABSTRACT Although survival rates for infants born extremely preterm (< 28 weeks’ gestation) have improved dramatically in recent decades, cognitive impairment remains a major concern. Adequate cognition is foundational for high quality of life and well-being. Compared to those born full term, extremely preterm children exhibit much higher rates of cognitive function impairment from early childhood through adulthood; and this is associated with neonatal inflammation. However, longitudinal research on cognitive function among extremely preterm children is limited. Little is known about how genetic and epigenetic factors are associated with trajectories of cognitive function, which can show longitudinal patterns such as downward/impaired, low-stable or upward-improvement. This raises a key unanswered question: are there genetic-epigenetic links to neonatal inflammation that predispose extremely preterm children to a particular trajectory of cognitive function? To address this question, we propose these specific aims: 1) Identify perinatal and neonatal immune factors predicting trajectories of cognitive function from ages 2 - 17 years among extremely preterm children; 2) Determine genetic variants and gene-by-neonatal inflammation mediation that predict trajectories of cognitive function; and 3) Examine whether DNA methylation modifies the effects of genetic variants and neonatal inflammation on trajectories of cognitive function. Our central hypothesis is that genetic variants of immune-related genes interact with neonatal immune factors to increase risk for a low-stable trajectory of cognitive function during childhood and adolescence. Additionally, we hypothesize that DNA methylation can mediate the effects of genetic variants to protect against the low-stable trajectory. These hypotheses are based on several preliminary findings from our team demonstrating that neonatal inflammation, as well as genetic and epigenetic factors regulating immune response, can influence cognitive function. This proposal leverages the Extremely Low Gestational Age Newborn (ELGAN) study, a multi-center cohort of extremely preterm children currently followed to age 15 years (N = 810), containing vast data on neurodevelopment and a unique biospecimen repository. Although ELGAN has DNA methylation data from placentas on a subset of the sample, we propose to use banked umbilical cord specimens for whole-genome genotyping and neonatal blood specimens for DNA methylation of the entire cohort. This proposal aligns with the scheduled ELGAN follow-up at 17 years of age to collect cognitive function data. This proposal has potential for significant impact on science and clinical practice related to cognitive function among extremely preterm children and is among the first to study relationships among genetic, epigenetic, immune factor and developmental trajectories of cognitive function. From this work, we can identify genes and mechanisms that can be used for risk stratification, as well as molecular processes that can be the targets of early risk-mitigating interventions to improve quality of life for children born extremely preterm. This information allows for targeted surveillance, preventative therapies and early intervention as soon after birth as possible.


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 = $312,179 )
2024	2024	UNIVERSITY OF MIAMI	1320 SOUTH DIXIE HIGHWAY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Nursing Research	000	5	7/19/2024	NON-COMPETING CONTINUATION	$312,179
														Subtotal = $312,179

Issue Date FY: 2023 ( Subtotal = $312,468 )
2023	2023	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Nursing Research	002	4	7/26/2023	NON-COMPETING CONTINUATION	$312,468
2023	2022	UNIVERSITY OF MIAMI	1320 SOUTH DIXIE HIGHWAY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Nursing Research	001	3	4/21/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$194,797
2023	2021	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Nursing Research	000	2	4/21/2023	NON-COMPETING CONTINUATION	-$194,797
														Subtotal = $312,468

Issue Date FY: 2022 ( Subtotal = $325,329 )
2022	2022	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Nursing Research	001	3	8/25/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$325,329
2022	2021	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Nursing Research	000	2	8/25/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $325,329

Issue Date FY: 2021 ( Subtotal = $385,574 )
2021	2021	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Nursing Research	000	2	7/20/2021	NON-COMPETING CONTINUATION	$385,574
														Subtotal = $385,574

Issue Date FY: 2020 ( Subtotal = $385,667 )
2020	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Nursing Research	000	1	9/10/2020	NEW	$385,667
														Subtotal = $385,667

Grand Total All Awards = $1,721,217

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Genetic and Epigenetic Effects on Childhood Cognitive Trajectories

Award Number: R01NR019245

ORGANIZATION: NATIONAL INSTITUTE OF NURSING RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer