Journal article
Maternal–fetal metabolic gene–gene interactions and risk of neural tube defects
Molecular genetics and metabolism, Vol.111(1), pp.46-51
01/2014
DOI: 10.1016/j.ymgme.2013.11.004
PMCID: PMC4394735
PMID: 24332798
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.
Details
- Title: Subtitle
- Maternal–fetal metabolic gene–gene interactions and risk of neural tube defects
- Creators
- Philip J Lupo - Department of Pediatrics, Section of Hematology–Oncology, Baylor College of Medicine, Houston, TX, USALaura E Mitchell - Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, TX, USAMark A Canfield - Texas Department of State Health Services, Austin, TX, USAGary M Shaw - Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USAAndrew F Olshan - Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USARichard H Finnell - Dell Pediatric Research Institute, Department of Nutritional Sciences, University of Texas at Austin, Austin, TX, USAHuiping Zhu - Dell Pediatric Research Institute, Department of Nutritional Sciences, University of Texas at Austin, Austin, TX, USANational Birth Defects Prevention Study
- Contributors
- Paul A Romitti (Contributor) - University of Iowa, Epidemiology
- Resource Type
- Journal article
- Publication Details
- Molecular genetics and metabolism, Vol.111(1), pp.46-51
- DOI
- 10.1016/j.ymgme.2013.11.004
- PMID
- 24332798
- PMCID
- PMC4394735
- NLM abbreviation
- Mol Genet Metab
- ISSN
- 1096-7192
- eISSN
- 1096-7206
- Publisher
- Elsevier Inc
- Grant note
- name: National Institute of Child Health and Development (NICHD), award: R21 HD 058912; DOI: 10.13039/100000030, name: Centers for Disease Control and Prevention, award: U50/CCU925286, U01/DD000494; name: NIH, award: R01 NS 050249; DOI: 10.13039/100000066, name: National Institute of Environmental Health Sciences, award: P30ES010126
- Language
- English
- Date published
- 01/2014
- Academic Unit
- Epidemiology; Biostatistics
- Record Identifier
- 9984213373802771
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