Gene-based analyses of the maternal genome implicate maternal effect genes as risk factors for conotruncal heart defects

PLoS One. 2020 Jun 9;15(6):e0234357. doi: 10.1371/journal.pone.0234357. eCollection 2020.


Congenital heart defects (CHDs) affect approximately 1% of newborns. Epidemiological studies have identified several genetically-mediated maternal phenotypes (e.g., pregestational diabetes, chronic hypertension) that are associated with the risk of CHDs in offspring. However, the role of the maternal genome in determining CHD risk has not been defined. We present findings from gene-level, genome-wide studies that link CHDs to maternal effect genes as well as to maternal genes related to hypertension and proteostasis. Maternal effect genes, which provide the mRNAs and proteins in the oocyte that guide early embryonic development before zygotic gene activation, have not previously been implicated in CHD risk. Our findings support a role for and suggest new pathways by which the maternal genome may contribute to the development of CHDs in offspring.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Child, Preschool
  • Family
  • Female
  • Genetic Testing / methods
  • Heart Defects, Congenital / etiology
  • Heart Defects, Congenital / genetics*
  • Humans
  • Hypertension / genetics
  • Infant
  • Infant, Newborn
  • Male
  • Maternal Exposure / adverse effects
  • Maternal Inheritance / genetics*
  • Middle Aged
  • Oocytes / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / genetics
  • Proteostasis / genetics
  • Risk Factors

Supplementary concepts

  • Conotruncal cardiac defects