ArticleMolecular genetics and metabolism2014
Maternal-fetal metabolic gene-gene interactions and risk of neural tube defects.
Article in Molecular genetics and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Original Findings and Updated Meta-Analysis for the Association Between Maternal Diabetes and Risk for Congenital Heart Disease Phenotypes.American journal of epidemiology · 2017Pooled it
- Maternal-fetal genetic interactions, imprinting, and risk of placental abruption.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2022Article
- Innovative approach to identify multigenomic and environmental interactions associated with birth defects in family-based hybrid designs.Genetic epidemiology · 2021Article
- Early Screening for Gestational Diabetes Using IADPSG Criteria May Be a Useful Predictor for Congenital Anomalies: Preliminary Data from a High-Risk Population.Journal of clinical medicine · 2020Article
- Mechanisms of Congenital Malformations in Pregnancies with Pre-existing Diabetes.Current diabetes reports · 2020Review
- Closing in on Mechanisms of Open Neural Tube Defects.Trends in neurosciences · 2020Review
- Digenic variants of planar cell polarity genes in human neural tube defect patients.Molecular genetics and metabolism · 2018Article
- Adipose Tissue Insulin Resistance in Gestational Diabetes.Metabolic syndrome and related disorders · 2017Article
- Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine.Scientific reports · 2016Article
- The Quantitative-MFG Test: A Linear Mixed Effect Model to Detect Maternal-Offspring Gene Interactions.Annals of human genetics · 2016Article
- Human Birth Weight and Reproductive Immunology: Testing for Interactions between Maternal and Offspring KIR and HLA-C Genes.Human heredity · 2016Article
- A Three-Way Interaction among Maternal and Fetal Variants Contributing to Congenital Heart Defects.Annals of human genetics · 2016Article
- Detecting gene-environment interactions in human birth defects: Study designs and statistical methods.Birth defects research. Part A, Clinical and molecular teratology · 2015Article
- Update on Prepregnancy Maternal Obesity: Birth Defects and Childhood Outcomes.Journal of pediatric genetics · 2015Review
- Association of facilitated glucose transporter 2 gene variants with the myelomeningocele phenotype.Birth defects research. Part A, Clinical and molecular teratology · 2015Article
- Intersection of complex genetic traits affecting maternal metabolism, fetal metabolism, and neural tube defect risk: looking for needles in multiple haystacks.Molecular genetics and metabolism · 2014Article
- Genetic, epigenetic, and environmental contributions to neural tube closure.Annual review of genetics · 2014Review
- Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Single-gene analyses indicate that maternal genes associated with metabolic conditions (e.g., obesity) may influence the risk of neural tube defects (NTDs). However, to our knowledge, there have been no assessments of maternal-fetal metabolic gene-gene interactions and NTDs. We investigated 23 single nucleotide polymorphisms among 7 maternal metabolic genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, and TCF7L2) and 2 fetal metabolic genes (SLC2A2 and UCP2). Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study for birth years 1999-2007. We used a 2-step approach to evaluate maternal-fetal gene-gene interactions. First, a case-only approach was applied to screen all potential maternal and fetal interactions (n = 76), as this design provides greater power in the assessment of gene-gene interactions compared to other approaches. Specifically, ordinal logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for each maternal-fetal gene-gene interaction, assuming a log-additive model of inheritance. Due to the number of comparisons, we calculated a corrected p-value (q-value) using the false discovery rate. Second, we confirmed all statistically significant interactions (q < 0.05) using a log-linear approach among case-parent triads. In step 1, there were 5 maternal-fetal gene-gene interactions with q < 0.05. The "top hit" was an interaction between maternal ENPP1 rs1044498 and fetal SLC2A2 rs6785233 (interaction OR = 3.65, 95% CI: 2.32-5.74, p = 2.09×10(-8), q=0.001), which was confirmed in step 2 (p = 0.00004). Our findings suggest that maternal metabolic genes associated with hyperglycemia and insulin resistance and fetal metabolic genes involved in glucose homeostasis may interact to increase the risk of NTDs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.