# The Maternal Genome and Risk of Structural Birth Defects

> **NIH NIH R03** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $149,950

## Abstract

Abstract
Birth defects are the leading cause of death in the first year of life, and a significant cause of morbidity and
mortality in all age groups. Structural malformations, such as congenital heart defects (CHDs), orofacial clefts
(OFC) and congenital diaphragmatic hernia (DH), comprise a significant portion of all birth defects: With a birth
prevalence of approximately 1%, CHDs alone account for up to a third of all birth defects. Since structural
malformations cannot be cured, primary prevention is an important goal. Progress towards prevention is,
however, impeded by gaps in knowledge about the causes of structural malformations. While studies of inherited
and de novo variants have begun to define the role of the embryonic genotype, much remains unknown about
the causes of these conditions. We believe that studies of the maternal genotype will help to fill this knowledge
gap. A role for the maternal genotype in determining the risk of structural malformations is supported by
epidemiologic evidence that genetically-mediated, maternal phenotypes are risk factors for structural
malformations. For example, maternal obesity is associated with increased risk of several malformations (i.e. it
is non-specific), including CHDs, OFC and DH. Further, studies have identified associations between structural
malformations and the maternal genotype for genes involved in folate metabolism (e.g. MTHFR) and for obesity
and diabetes-related genes (e.g. UCP2). In addition, our preliminary data provide novel evidence that maternal
effect genes (MEGs), which encode the maternal transcripts and proteins in the oocyte that direct development
prior to the activation of the embryonic genome, are also related to the risk of structural malformations. Our long-
term goal is to identify the causes of structural malformations and to translate this knowledge into prevention
strategies. Our objective in this study is to leverage the resources provided by the Gabriella Miller Kid's First
initiative to identify maternal genes associated with structural malformations. Our working hypotheses for the
proposed studies are: 1. Maternal genotypes for MEG variants (common and rare) are associated with structural
malformations; 2. There are additional, as yet unidentified, genes that are associated with risk of structural
malformations via the maternal genotype; and 3. The effects of the maternal genotype are non-specific and,
therefore, contribute to the risk of multiple different structural malformations. We will achieve our objective with
these aims: Aim 1. Identify maternal genes and variants associated with CHD, OFC, and DH; Aim 2. Identify
maternal genes and variants affecting multiple structural malformations; Aim 3. Identify maternal genes affecting
structural malformations through expression levels. The proposed studies are focused on computational and
statistical analyses of existing data for test of novel and significant biological hypotheses that have not been fully
exp...

## Key facts

- **NIH application ID:** 9949423
- **Project number:** 5R03HD098552-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Goo Jun
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $149,950
- **Award type:** 5
- **Project period:** 2019-06-10 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949423

## Citation

> US National Institutes of Health, RePORTER application 9949423, The Maternal Genome and Risk of Structural Birth Defects (5R03HD098552-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9949423. Licensed CC0.

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