Open AccessGene-based analyses of the maternal genome implicate maternal effect genes as risk factors for conotruncal heart defects
Author(s) -
Anshuman Sewda,
A. J. Agopian,
Elizabeth Goldmuntz,
Hákon Hákonarson,
Bernice E. Morrow,
Fadi I Musfee,
Deanne Taylor,
Laura E. Mitchell
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0234357
Subject(s) - offspring , biology , gene , genetics , phenotype , genome , proteostasis , genome wide association study , pregnancy , bioinformatics , single nucleotide polymorphism , genotype
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.