Abstract
The recent focus on the role of epigenetic mechanisms in mental health has led to several studies examining the association of epigenetic processes with psychiatric conditions and neurodevelopmental traits. Some studies suggest that epigenetic changes might be causal in the development of the psychiatric condition under investigation. However, other scenarios are possible, e.g., statistical confounding or reverse causation, making it particularly challenging to derive conclusions on causality. In the present review, we examine the evidence from human population studies for a possible role of epigenetic mechanisms in neurodevelopment and mental health and discuss methodological approaches on how to strengthen causal inference, including the need for replication, (quasi-)experimental approaches and Mendelian randomization. We signpost openly accessible resources (e.g., “MR-Base” “EWAS catalog” as well as tissue-specific methylation and gene expression databases) to aid the application of these approaches.
Highlights
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK
Of the known epigenetic processes involved in gene regulation, DNA methylation, which consists of the covalent addition of a methyl group to a cytosine base at CpG dinucleotides, is the most widely studied
Epidemiological studies that have investigated the association of DNA methylation with mental health traits and conditions in peripheral blood or saliva using the Illumina 450K arrays were identified in a semi-systemic manner by searching within PubMed
Summary
Mental health and neurodevelopmental disorders are under the influence of both genetic and environmental factors. Epigenetic mechanisms regulate gene expression and are potential mediators of both these genetic and environmental effects on mental traits and disorders. DNA methylation at the genome-wide level using Illumina Infinium 450K or EPIC arrays in peripheral blood or saliva samples, since these tissues are most commonly available in large studies. While this search is not meant as a systematic review, it provides examples of studies that investigated the link between DNA methylation and brain-related processes in peripheral tissues.
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