TY - JOUR
T1 - Gene-based analyses of the maternal genome implicate maternal effect genes as risk factors for conotruncal heart defects
AU - Pediatric Cardiac Genomics Consortium
AU - Sewda, Anshuman
AU - Agopian, A. J.
AU - Goldmuntz, Elizabeth
AU - Hakonarson, Hakon
AU - Morrow, Bernice E.
AU - Musfee, Fadi
AU - Taylor, Deanne
AU - Mitchell, Laura E.
N1 - Funding Information:
This work was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD070454, AJA, EG, BM, LEM, FM, AS, DT; R21HD097347, AJA, LEM; R03HD098552, LEM) (https://www.nichd.nih.gov/), the National Heart, Lung, and Blood Institute (P50-HL74731) (https:// www.nhlbi.nih.gov/), including the PCGC (U01-HL098188, U01HL131003, U01-HL098147, U01-HL098153, U01-HL098163, U01-HL098123, U01-HL098162) (https://benchtobassinet.com) and the Cardiovascular Development Consortium (U01-HL098166) (https://benchtobassinet.com/?page-id=1644), as well as the National Human Genome Research Institute (U54HG006504) (https://www. genome.gov), and the National Center for Research Resources (M01-RR-000240, RR024134, which is now the National Center for Advancing Translational Sciences (UL1TR000003) (https:// ncats.nih.gov). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding sources. Array genotyping of the CHOP cohorts was funded by an Institutional Development Fund to The Center for Applied Genomics from The Children's Hospital of Philadelphia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2020 Sewda et al.
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0234357
DO - 10.1371/journal.pone.0234357
M3 - Article
C2 - 32516339
AN - SCOPUS:85086355969
SN - 1932-6203
VL - 15
JO - PLoS One
JF - PLoS One
IS - 6
M1 - e0234357
ER -
