ArticleHuman molecular genetics2017
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.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 6 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 6 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review.European journal of epidemiology · 2024Pooled it
- A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation.Epigenetics · 2023Pooled it
- Prenatal medication exposure and epigenetic outcomes: a systematic literature review and recommendations for prenatal pharmacoepigenetic studies.Epigenetics · 2022Pooled it
- DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts.Clinical epigenetics · 2021Pooled it
- 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
- Immunosuppressant Use Mediates Neuroprotection Against Alzheimer's Disease in Rheumatoid Arthritis-A Two-Step Mendelian Randomization and NHANES Study.International journal of rheumatic diseases · 2026Article
- Population epigenetics: deciphering DNA methylation diversity and its implications for health, disease, and evolution.Molecular biology and evolution · 2026Review
- Prenatal Vitamin B12 and Children's Brain Development and Cognitive, Language and Motor Outcomes: A Scoping Review.Children (Basel, Switzerland) · 2024Article
- Linking Prenatal Environmental Exposures to Lifetime Health with Epigenome-Wide Association Studies: State-of-the-Science Review and Future Recommendations.Environmental health perspectives · 2023Review
- Epigenetics applied to child and adolescent mental health: Progress, challenges and opportunities.JCPP advances · 2023Article
- Folate and vitamin B12 status: associations with maternal glucose and neonatal DNA methylation sites related to dysglycaemia, in pregnant women with obesity.Journal of developmental origins of health and disease · 2022Article
- Children's Greenness Exposure and IQ-Associated DNA Methylation: A Prospective Cohort Study.International journal of environmental research and public health · 2021Article
- Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study.BMC pulmonary medicine · 2020Article
- Statin Use Associates With Risk of Type 2 Diabetes via Epigenetic Patterns atFrontiers in genetics · 2020Article
- Methylomic profiling in trisomy 21 identifies cognition- and Alzheimer's disease-related dysregulation.Clinical epigenetics · 2019Article
- DNA Methylation and Type 2 Diabetes: the Use of Mendelian Randomization to Assess Causality.Current genetic medicine reports · 2019Article
- Epigenetics and gestational diabetes: a review of epigenetic epidemiology studies and their use to explore epigenetic mediation and improve prediction.Diabetologia · 2019Review
- Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study.Human molecular genetics · 2019Article
- What genome-wide association studies reveal about the association between intelligence and physical health, illness, and mortality.Current opinion in psychology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
An adequate intake of vitamin B12 during pregnancy plays an important role in offspring neurodevelopment, potentially via epigenetic processes. We used a two-step Mendelian randomization approach to assess whether DNA methylation plays a mediating and causal role in associations between maternal vitamin B12 status and offspring's cognition. Firstly, we estimated the causal effect of maternal vitamin B12 levels on cord blood DNA methylation using the maternal FUT2 genotypes rs492602:A > G and rs1047781:A > T as proxies for circulating vitamin B12 levels in the Avon Longitudinal Study of Parents and Children (ALSPAC) and we tested the observed associations in a replication cohort. Secondly, we estimated the causal effect of DNA methylation on IQ using the offspring genotype at sites close to the methylated CpG site as a proxy for DNA methylation in ALSPAC and in a replication sample. The first step Mendelian randomization estimated that maternal vitamin B12 had a small causal effect on DNA methylation in offspring at three CpG sites, which was replicated for one of the sites. The second step Mendelian randomization found weak evidence of a causal effect of DNA methylation at two of these sites on childhood performance IQ which was replicated for one of the sites. The findings support a causal effect of maternal vitamin B12 levels on cord blood DNA methylation, and a causal effect of vitamin B12-responsive DNA methylation changes on children's cognition. Some limitations were identified and future studies using a similar approach should aim to overcome such issues.
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Registered trials
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