# Characterizing the functional genomic atlas of human placenta and unveiling the prenatal programming of early-life development

> **NIH NIH R01** · EMORY UNIVERSITY · 2023 · $729,926

## Abstract

SUMMARY/ABSTRACT
A substantial proportion of postnatal health, including childhood obesity and metabolic disease, is programmed
in utero during fetal development. While birthweight has been linked to these outcomes, it may be only a proxy
reflecting a complex interplay of genetics and environment that defines a common etiology between birthweight
and later life health, and which defines the Developmental Origins of Heath and Disease (DOHaD) hypothesis.
Supporting this hypothesis are a number of large, genome-wide association studies (GWAS) that have
identified genetic variants associated with early life outcomes, such as birthweight and childhood obesity, body
mass index and adiposity, and have demonstrated that these same variants can also impact adult
cardiovascular traits and disease. Thus, early intervention, either through identifying at-risk population and/or
targeting functional variations induced by genetic and environmental factors, could be highly effective in
reducing overall disease burden. Our team spearheaded the placental research suggesting that the placenta
may be the critical organ for much of childhood health programming. This proposal is framed on the
hypothesis that the functional genome of a placenta acts as a critical and unique mediator of the in utero
environment (both genetic and non-genetic) to influence birthweight and program postnatal growth and
development, and such effects may occur in particular cellular components of the placenta. Leveraging the
resources of three well-characterized and diverse birth cohorts in the US, we propose a rigorous integrative
genomics and systems biology investigation to demonstrate the causal, mechanistic role of the placenta in
postnatal health programming using state-of-the-art, post-GWAS, functional genomic investigations, including
innovative use of single-nucleus RNA sequencing technology and molecular quantitative trait loci analyses
(molQTL). We will build a comprehensive molecular atlas of human term placenta to identify functional
molecular features that mediate birthweight GWAS hits as well as those independent of genetics, and we will
build a placental transcriptomic atlas at cellular resolution to improve mechanistic understanding of the role of
the placenta at the single cell level. Furthermore, we will examine prospective associations of the birthweight-
related molecular features in placenta with growth trajectory, childhood obesity, BMI, and adiposity at age 5 as
a model of the placenta’s role in long-term health programming. This project aligns with the research priorities
of Pregnancy and Perinatology Branch of the NICHD, in defining “molecular biology processes involved in
normal and abnormal placentation” as well as “genetic and epigenetic factors that adversely affect pregnancy
outcomes”. Results from our study will pave the way for the development of placenta-based biomarkers to be
assessed at birth for prospective risk stratification into childhood so early inter...

## Key facts

- **NIH application ID:** 10580294
- **Project number:** 1R01HD108310-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Jia Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $729,926
- **Award type:** 1
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10580294

## Citation

> US National Institutes of Health, RePORTER application 10580294, Characterizing the functional genomic atlas of human placenta and unveiling the prenatal programming of early-life development (1R01HD108310-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10580294. Licensed CC0.

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