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

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $134,714

## Abstract

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.

## Key facts

- **NIH application ID:** 10214809
- **Project number:** 3R01HD098232-02S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Liming Liang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $134,714
- **Award type:** 3
- **Project period:** 2019-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214809

## Citation

> US National Institutes of Health, RePORTER application 10214809, Inter-generational Link of Cardio-Metabolic Risk:  Integrate Multi-OMICs with Birth Cohort (3R01HD098232-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10214809. Licensed CC0.

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