Epigenetic epidemiology of common complex disease: prospects for prediction, prevention, and treatment

Research output: Contribution to journalArticle (Academic Journal)peer-review

153 Citations (Scopus)

Abstract

The epigenome records a variety of dietary, lifestyle, behavioral, and social cues, providing an interface between the environment and the genome. Epigenetic variation, whether genetically or environmentally determined, contributes to inter-individual variation in gene expression and thus to variation in common complex disease risk. Interventions based upon epigenetic agents, including DNA methyltransferase inhibitors and histone deacetylase inhibitors, have been in clinical use for many years, but their role outside treatment of specific cancers is not established. Epigenetic therapies will only be fruitful if epigenetic mechanisms are causally related to the disease being treated. Evidence linking epigenetic variation to specific disease phenotypes to date is lacking. Epidemiological approaches can be applied to help separate causal from non-causal associations. We propose the development of a Mendelian randomization approach (“genetical epigenomics”), which could help overcome the problems of confounding and reverse causation (when an association between epigenetic patterns and disease phenotype is observed but it is unknown whether the disease is causing changes to the epigenome or epigenetic changes are causal in disease pathogenesis).
Original languageEnglish
Article numbere1000356
Number of pages8
JournalPLoS Medicine
Volume7
Issue number10
DOIs
Publication statusPublished - 26 Oct 2010

Keywords

  • Disease
  • Epigenesis, Genetic
  • Humans
  • Metagenomics
  • Models, Biological
  • Molecular Epidemiology
  • Preventive Medicine
  • Prognosis
  • Rare Diseases
  • Therapeutics
  • Translational Medical Research

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