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

Lookup NU author(s): Professor Caroline Relton

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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.

Publication metadata

Author(s): Kirkbride JB, Susser E, Kundakovic M, Kresovich JK, Smith GD, Relton CL

Publication type: Article

Publication status: Published

Journal: Epigenomics

Year: 2012

Volume: 4

Issue: 3

Pages: 303-315

Print publication date: 01/06/2012

ISSN (print): 1750-1911

ISSN (electronic): 1750-192X

Publisher: Future Medicine Ltd.

URL: http://dx.doi.org/10.2217/EPI.12.20

DOI: 10.2217/EPI.12.20

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