Journal article
Paternal genetic variants and risk of obstructive heart defects: A parent-of-origin approach
PLoS genetics, Vol.17(3), pp.e1009413-e1009413
03/2021
DOI: 10.1371/journal.pgen.1009413
PMCID: PMC7971842
PMID: 33684136
Abstract
Previous research on risk factors for obstructive heart defects (OHDs) focused on maternal and infant genetic variants, prenatal environmental exposures, and their potential interaction effects. Less is known about the role of paternal genetic variants or environmental exposures and risk of OHDs. We examined parent-of-origin effects in transmission of alleles in the folate, homocysteine, or transsulfuration pathway genes on OHD occurrence in offspring. We used data on 569 families of liveborn infants with OHDs born between October 1997 and August 2008 from the National Birth Defects Prevention Study to conduct a family-based case-only study. Maternal, paternal, and infant DNA were genotyped using an Illumina Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR), 95% confidence interval (CI), and likelihood ratio tests from log-linear models were used to estimate the parent-of-origin effect of 877 SNPs in 60 candidate genes in the folate, homocysteine, and transsulfuration pathways on the risk of OHDs. Bonferroni correction was applied for multiple testing. We identified 3 SNPs in the transsulfuration pathway and 1 SNP in the folate pathway that were statistically significant after Bonferroni correction. Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively, compared to infants who inherited maternally-derived copies of the same alleles. We observed statistically significant decreased risk of OHDs among infants who inherited paternal gene variants involved in folate and transsulfuration pathways.
Details
- Title: Subtitle
- Paternal genetic variants and risk of obstructive heart defects: A parent-of-origin approach
- Creators
- Jenil Patel - Department of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Dallas, TX, United States of AmericaEmine Bircan - Arkansas Center for Birth Defects Research and Prevention, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States of AmericaXinyu Tang - Biostatistics Program, Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Arkansas Children's Research Institute, Little Rock, AR, United States of AmericaMohammed Orloff - Arkansas Center for Birth Defects Research and Prevention, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States of AmericaCharlotte A Hobbs - Rady Children's Institute for Genomic Medicine, San Diego, CA, United States of AmericaMarilyn L Browne - Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY, United States of AmericaLorenzo D Botto - Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, UT, United States of AmericaRichard H Finnell - Department of Molecular and Cellular Biology, Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX, United States of AmericaMary M Jenkins - National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, United States of AmericaAndrew Olshan - Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of AmericaPaul A Romitti - Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IA, United States of AmericaGary M Shaw - Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, United States of AmericaMartha M Werler - Department of Epidemiology, School of Public Health, Boston University, Boston, MA, United States of AmericaJingyun Li - Biostatistics Program, Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Arkansas Children's Research Institute, Little Rock, AR, United States of AmericaWendy N Nembhard - Arkansas Center for Birth Defects Research and Prevention, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States of AmericaNational Birth Defects Prevention Study
- Resource Type
- Journal article
- Publication Details
- PLoS genetics, Vol.17(3), pp.e1009413-e1009413
- DOI
- 10.1371/journal.pgen.1009413
- PMID
- 33684136
- PMCID
- PMC7971842
- NLM abbreviation
- PLoS Genet
- ISSN
- 1553-7390
- eISSN
- 1553-7404
- Publisher
- Public Library Science
- Grant note
- U01 DD001229 / NCBDD CDC HHS R01 HD039054 / NICHD NIH HHS CDC HHS U01 DD001227 / NCBDD CDC HHS U01 DD001039 / NCBDD CDC HHS P30 ES030285 / NIEHS NIH HHS U54 TR001629 / NCATS NIH HHS U01 DD001226 / NCBDD CDC HHS U01 DD001285 / NCBDD CDC HHS
- Language
- English
- Date published
- 03/2021
- Academic Unit
- Epidemiology; Biostatistics
- Record Identifier
- 9984214703402771
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