ArticleBMC bioinformatics2013
The causal effect of red blood cell folate on genome-wide methylation in cord blood: a Mendelian randomization approach.
Article in BMC bioinformatics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
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Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- Mendelian randomisation approaches to the study of prenatal exposures: A systematic review.Paediatric and perinatal epidemiology · 2021Pooled it
- Mendelian Randomization and the Environmental Epigenetics of Health: a Systematic Review.Current environmental health reports · 2019Pooled it
- A Methylome-Wide Association Study of Trajectories of Oppositional Defiant Behaviors and Biological Overlap With Attention Deficit Hyperactivity Disorder.Child development · 2018Article
- Inflammation-related epigenetic risk and child and adolescent mental health: A prospective study from pregnancy to middle adolescence.Development and psychopathology · 2018Article
- Exploring a causal role of DNA methylation in the relationship between maternal vitamin B12 during pregnancy and child's IQ at age 8, cognitive performance and educational attainment: a two-step Mendelian randomization study.Human molecular genetics · 2017Article
- Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children's Environmental Health Studies: The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group.Environmental health perspectives · 2017Article
- Contrasting the effects of intra-uterine smoking and one-carbon micronutrient exposures on offspring DNA methylation.Epigenomics · 2017Review
- Genomics, Telomere Length, Epigenetics, and Metabolomics in the Nurses' Health Studies.American journal of public health · 2016Review
- The Role of DNA Methylation in Cardiovascular Risk and Disease: Methodological Aspects, Study Design, and Data Analysis for Epidemiological Studies.Circulation research · 2016Review
- Exploring possible epigenetic mediation of early-life environmental exposures on adiposity and obesity development.International journal of epidemiology · 2015Review
- Approaches for drawing causal inferences from epidemiological birth cohorts: a review.Early human development · 2014Review
- Genome-wide DNA methylation profiling identifies a folate-sensitive region of differential methylation upstream of ZFP57-imprinting regulator in humans.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- On the potential of models for location and scale for genome-wide DNA methylation data.BMC bioinformatics · 2014Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundInvestigation of the biological mechanism by which folate acts to affect fetal development can inform appraisal of expected benefits and risk management. This research is ethically imperative given the ubiquity of folic acid fortified products in the US. Considering that folate is an essential component in the one-carbon metabolism pathway that provides methyl groups for DNA methylation, epigenetic modifications provide a putative molecular mechanism mediating the effect of folic acid supplementation on neonatal and pediatric outcomes.
resultsIn this study we use a Mendelian Randomization Unnecessary approach to assess the effect of red blood cell (RBC) folate on genome-wide DNA methylation in cord blood. Site-specific CpG methylation within the proximal promoter regions of approximately 14,500 genes was analyzed using the Illumina Infinium Human Methylation27 Bead Chip for 50 infants from the Epigenetic Birth Cohort at Brigham and Women's Hospital in Boston. Using methylenetetrahydrofolate reductase genotype as the instrument, the Mendelian Randomization approach identified 7 CpG loci with a significant (mostly positive) association between RBC folate and methylation level. Among the genes in closest proximity to this significant subset of CpG loci, several enriched biologic processes were involved in nucleic acid transport and metabolic processing. Compared to the standard ordinary least squares regression method, our estimates were demonstrated to be more robust to unmeasured confounding.
conclusionsTo the authors' knowledge, this is the largest genome-wide analysis of the effects of folate on methylation pattern, and the first to employ Mendelian Randomization to assess the effects of an exposure on epigenetic modifications. These results can help guide future analyses of the causal effects of periconceptional folate levels on candidate pathways.
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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.