Title | Gene-based analyses of the maternal genome implicate maternal effect genes as risk factors for conotruncal heart defects. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Sewda, A, Agopian, AJ, Goldmuntz, E, Hakonarson, H, Morrow, BE, Musfee, F, Taylor, D, Mitchell, LE |
Corporate Authors | Pediatric Cardiac Genomics Consortium |
Journal | PLoS One |
Volume | 15 |
Issue | 6 |
Pagination | e0234357 |
Date Published | 2020 |
ISSN | 1932-6203 |
Keywords | Adult, Case-Control Studies, Child, Preschool, Family, Female, Genetic Testing, Heart Defects, Congenital, Humans, Hypertension, Infant, Infant, Newborn, Male, Maternal Exposure, Maternal Inheritance, Middle Aged, Oocytes, Pregnancy, Prenatal Exposure Delayed Effects, Proteostasis, Risk Factors |
Abstract | 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. |
DOI | 10.1371/journal.pone.0234357 |
Alternate Journal | PLoS One |
PubMed ID | 32516339 |
PubMed Central ID | PMC7282656 |
Grant List | U01 HL131003 / HL / NHLBI NIH HHS / United States U01 HL098123 / HL / NHLBI NIH HHS / United States P01 HD070454 / HD / NICHD NIH HHS / United States R21 HD097347 / HD / NICHD NIH HHS / United States U01 HL098147 / HL / NHLBI NIH HHS / United States U01 HL098163 / HL / NHLBI NIH HHS / United States UL1 TR000003 / TR / NCATS NIH HHS / United States U54 HD086984 / HD / NICHD NIH HHS / United States R03 HD098552 / HD / NICHD NIH HHS / United States U54 HG006504 / HG / NHGRI NIH HHS / United States U01 HL098162 / HL / NHLBI NIH HHS / United States U01 HL098166 / HL / NHLBI NIH HHS / United States M01 RR000240 / RR / NCRR NIH HHS / United States U01 HL098153 / HL / NHLBI NIH HHS / United States P50 HL074731 / HL / NHLBI NIH HHS / United States U01 HL098188 / HL / NHLBI NIH HHS / United States |