# Maternal Genes that Control Early Embryonic Development as Risk Factors for Congenital Heart Defects

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $238,587

## Abstract

Project Summary/Abstract
With a birth prevalence of approximately 1/100, congenital heart defects (CHDs) are the most common birth
defects and the leading cause of birth defect related infant mortality. CHDs cannot be cured and there are no
population-based prevention strategies. Further, the specific causes of most CHDs are unknown. The gaps in
our understanding of the causes of CHDs hamper our ability to prevent CHDs. Hence, the long-term goal of our
research is to identify the causes of CHDs and to use this knowledge to develop CHD prevention strategies. To
this end, we conducted a gene-level, genome-wide association study of conotruncal heart defects (CTDs) and
the maternal genotype. The results of this study suggest the novel hypothesis that the maternal genotype
influences embryonic heart development via maternal gene products present in the oocyte that direct early
embryonic development. Maternal genes that affect embryonic development in this way are called maternal
effect genes (MEGs). In our study, there was a 2-3 fold enrichment of mammalian MEGs among the maternal
genes that were most significantly associated with CTDs (p<0.05). Our objective in this proposal is to identify the
specific MEGs, and the variants within these MEGs, that are associated with CTDs. Specifically, our working
hypothesis for the proposed studies is that maternal genotypes for a subset of MEGs are associated with the
risk of CTDs and these associations extend to other types of CHDs, specifically left-sided cardiac lesions (LSLs).
We will achieve our aims through secondary analyses of data from three large, independent, study cohorts: 1465
case-parent trios (670 CTD1; 478 CTD2; 317 LSLs) from the Children’s Hospital of Philadelphia; and 547 trios
(355 CTDs, 192 LSLs) from the Pediatric Cardiac Genomics Consortium. In Aim 1, we will identify the specific
MEGs, and the variants within these MEGs, that are driving the observed MEG enrichment. In Aim 2, we will
evaluate MEGs in LSLs, to establish the specificity of MEG-CTD associations. In summary, our preliminary data
provide support for a novel hypothesis about the role of the maternal genotype in the development of CHDs in
offspring. Confirmation of this hypothesis would provide new insight into the causes of CHDs and, perhaps, other
structural birth defects. Hence, the studies proposed in this application have the potential to significantly affect
the fields of birth defect epidemiology and genetics, as well as public health efforts to prevent birth defects.

## Key facts

- **NIH application ID:** 9982092
- **Project number:** 5R21HD097347-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** LAURA E. MITCHELL
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $238,587
- **Award type:** 5
- **Project period:** 2019-07-20 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982092

## Citation

> US National Institutes of Health, RePORTER application 9982092, Maternal Genes that Control Early Embryonic Development as Risk Factors for Congenital Heart Defects (5R21HD097347-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982092. Licensed CC0.

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