Prenatal nutrition, epigenetics and schizophrenia risk: can we test causal effects?

James B. Kirkbride*, Ezra Susser, Marija Kundakovic, Jacob K. Kresovich, George Davey Smith, Caroline L. Relton

*Corresponding author for this work

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

63 Citations (Scopus)

Abstract

We posit that maternal prenatal nutrition can influence offspring schizophrenia risk via epigenetic effects. In this article, we consider evidence that prenatal nutrition is linked to epigenetic outcomes in offspring and schizophrenia in offspring, and that schizophrenia is associated with epigenetic changes. We focus upon one-carbon metabolism as a mediator of the pathway between perturbed prenatal nutrition and the subsequent risk of schizophrenia. Although post-mortem human studies demonstrate DNA methylation changes in brains of people with schizophrenia, such studies cannot establish causality. We suggest a testable hypothesis that utilizes a novel two-step Mendelian randomization approach, to test the component parts of the proposed causal pathway leading from prenatal nutritional exposure to schizophrenia. Applied here to a specific example, such an approach is applicable for wider use to strengthen causal inference of the mediating role of epigenetic factors linking exposures to health outcomes in population-based studies.

Original languageEnglish
Pages (from-to)303-315
Number of pages13
JournalEpigenomics
Volume4
Issue number3
DOIs
Publication statusPublished - Jun 2012

Keywords

  • Agouti
  • DNA methylation
  • epigenetic epidemiology
  • folate
  • Mendelian randomization
  • one-carbon metabolism
  • prenatal nutrition
  • psychosis
  • Reelin
  • schizophrenia
  • NEURAL-TUBE DEFECTS
  • MATERNAL METHYL SUPPLEMENTS
  • GENOMIC DNA METHYLATION
  • AGOUTI GENE-EXPRESSION
  • FOLIC-ACID USE
  • BIPOLAR DISORDER
  • BIRTH-COHORT
  • MENDELIAN RANDOMIZATION
  • ADULT SCHIZOPHRENIA
  • MONOZYGOTIC TWINS

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