Effect of parental origin of damaging variants in pro-angiogenic genes on fetal growth in patients with congenital heart defects: Data and analyses.
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ABSTRACT:
SUBMITTER: Russell MW
PROVIDER: S-EPMC6700409 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
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Effect of parental origin of damaging variants in pro-angiogenic genes on fetal growth in patients with congenital heart defects: Data and analyses.
Russell Mark W MW Moldenhauer Julie S JS Rychik Jack J Burnham Nancy B NB Zullo Erin E Parry Samuel I SI Simmons Rebecca A RA Elovitz Michal A MA Nicolson Susan C SC Linn Rebecca L RL Johnson Mark P MP Yu Sunkyung S Sampson Matthew G MG Hakonarson Hakon H Gaynor J William JW
Data in brief 20190726
The placenta is a highly vascular structure composed of both maternal and fetal elements. We have determined that damaging variants in genes responsible for the positive regulation of angiogenesis (PRA) (GO:0045766) that are inherited by the fetus impair fetal growth and placental function in pregnancies involving critical congenital cardiac defects (Russell et al., 2019). In this dataset, we present the specific genetic variants identified, describe the parental origin of each variant where pos ...[more]
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Project description:BackgroundMaternal and inherited (ie, case) genetic factors likely contribute to the pathogenesis of congenital heart defects, but it is unclear whether individual common variants confer a large risk.Methods and resultsTo evaluate the relationship between individual common maternal/inherited genotypes and risk for heart defects, we conducted genome-wide association studies in 5 cohorts. Three cohorts were recruited at the Children's Hospital of Philadelphia: 670 conotruncal heart defect (CTD) case-parent trios, 317 left ventricular obstructive tract defect (LVOTD) case-parent trios, and 406 CTD cases (n=406) and 2976 pediatric controls. Two cohorts were recruited through the Pediatric Cardiac Genomics Consortium: 355 CTD trios and 192 LVOTD trios. We also conducted meta-analyses using the genome-wide association study results from the CTD cohorts, the LVOTD cohorts, and from the combined CTD and LVOTD cohorts. In the individual genome-wide association studies, several genome-wide significant associations (P≤5×10-8) were observed. In our meta-analyses, 1 genome-wide significant association was detected: the case genotype for rs72820264, an intragenetic single-nucleotide polymorphism associated with LVOTDs (P=2.1×10-8).ConclusionsWe identified 1 novel candidate region associated with LVOTDs and report on several additional regions with suggestive evidence for association with CTD and LVOTD. These studies were constrained by the relatively small samples sizes and thus have limited power to detect small to moderate associations. Approaches that minimize the multiple testing burden (eg, gene or pathway based) may, therefore, be required to uncover common variants contributing to the risk of these relatively rare conditions.
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