ArticlePloS one2012
Prenatal famine and genetic variation are independently and additively associated with DNA methylation at regulatory loci within IGF2/H19.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.
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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
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 146 citations in OpenAlex.
- The association between prenatal famine, DNA methylation and mental disorders: a systematic review and meta-analysis.Clinical epigenetics · 2023Pooled it
- Epigenetics and human obesity.International journal of obesity (2005) · 2015Pooled it
- Trial
- The Potential Physiologic Mechanisms by Which Early-Life Nutrition May Influence Type 2 Diabetes Pathophysiology in Humans.Annual review of nutrition · 2026Review
- Review
- Prenatal famine exposure restricts genetic effects on birth weight with implications for metabolic disease risk.Communications medicine · 2026Article
- Detection of DNA methylation from buccal swabs using nanopore sequencing to study stunting.Epigenetics · 2024Article
- Epigenetic developmental mechanisms underlying sex differences in cancer.The Journal of clinical investigation · 2024Review
- Article
- Maternal Periconceptional Folic Acid Supplementation and DNA Methylation Patterns in Adolescent Offspring.The Journal of nutrition · 2023Article
- Article
- Article
- Prenatal arsenic exposure induces immunometabolic alteration and renal injury in rats.Frontiers in medicine · 2022Article
- Centenarians exposed to the Spanish flu in their early life better survived to COVID-19.Aging · 2021Article
- DNA methylation differences at birth after conception through ART.Human reproduction (Oxford, England) · 2021Article
- Prenatal famine exposure and adult health outcomes: an epigenetic link.Environmental epigenetics · 2021Review
- Methylation of a newly identified region of the INS-IGF2 gene determines IGF2 expression in breast cancer tumors and in breast cancer cells.Oncotarget · 2020Article
- The role of environmental exposures and the epigenome in health and disease.Environmental and molecular mutagenesis · 2020Review
- Differential methylation of enhancer at IGF2 is associated with abnormal dopamine synthesis in major psychosis.Nature communications · 2019Article
- Neonatal bloodspot DNA methylation patterns are associated with childhood weight status in the Healthy Families Project.Pediatric research · 2019Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Both the early environment and genetic variation may affect DNA methylation, which is one of the major molecular marks of the epigenome. The combined effect of these factors on a well-defined locus has not been studied to date. We evaluated the association of periconceptional exposure to the Dutch Famine of 1944-45, as an example of an early environmental exposure, and single nucleotide polymorphisms covering the genetic variation (tagging SNPs) with DNA methylation at the imprinted IGF2/H19 region, a model for an epigenetically regulated genomic region. DNA methylation was measured at five differentially methylated regions (DMRs) that regulate the imprinted status of the IGF2/H19 region. Small but consistent differences in DNA methylation were observed comparing 60 individuals with periconceptional famine exposure with unexposed same-sex siblings at all IGF2 DMRs (P(BH)<0.05 after adjustment for multiple testing), but not at the H19 DMR. IGF2 DMR0 methylation was associated with IGF2 SNP rs2239681 (P(BH) = 0.027) and INS promoter methylation with INS SNPs, including rs689, which tags the INS VNTR, suggesting a mechanism for the reported effect of the VNTR on INS expression (P(BH) = 3.4 × 10(-3)). Prenatal famine and genetic variation showed similar associations with IGF2/H19 methylation and their contributions were additive. They were small in absolute terms (<3%), but on average 0.5 standard deviations relative to the variation in the population. Our analyses suggest that environmental and genetic factors could have independent and additive similarly sized effects on DNA methylation at the same regulatory site.
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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.