Epigenetics in eating disorders: a systematic review

Abstract

Eating disorders are complex heritable conditions influenced by both genetic and environmental factors. Given the progress of genomic discovery in anorexia nervosa, with the identification of the first genome-wide significant locus, as well as animated discussion of epigenetic mechanisms in linking environmental factors with disease onset, our goal was to conduct a systematic review of the current body of evidence on epigenetic factors in eating disorders to inform future directions in this area. Following PRISMA guidelines, two independent authors conducted a search within PubMed and Web of Science and identified 18 journal articles and conference abstracts addressing anorexia nervosa (n = 13), bulimia nervosa (n = 6), and binge-eating disorder (n = 1), published between January 2003 and October 2017. We reviewed all articles and included a critical discussion of field-specific methodological considerations. The majority of epigenetic analyses of eating disorders investigated methylation at candidate genes (n = 13), focusing on anorexia and bulimia nervosa in very small samples with considerable sample overlap across published studies. Three studies used microarray-based technologies to examine DNA methylation across the genome of anorexia nervosa and binge-eating disorder patients. Overall, results were inconclusive and were primarily exploratory in nature. The field of epigenetics in eating disorders remains in its infancy. We encourage the scientific community to apply methodologically sound approaches using genome-wide designs including epigenome-wide association studies (EWAS), to increase sample sizes, and to broaden the focus to include all eating disorder types.

Figure 1

The epigenetic profile of a human cell comprises several epigenetic mechanisms: a) DNA methylation is the most prominent and prevalent DNA modification characterized by an addition of of a methyl-group to cytosine in the context of cytosine-guanine dinucleotides (i.e., CpG sites). b) Histone proteins compact chromosomal DNA in the nucleus of the cell and regulate gene expression and histone modifications are chemical modifications to the N-terminal histone tails, which extend out of the nucleosome complex (i.e., the transcription apparatus). An increasing number of modifications to amino acids in the histone tails are being identified, including methylation, acetylation, and phosphorylation. These modifications are characterized by tissue specificity and are highly correlated with different transcriptional chromatin states. c) Non-coding RNAs are expressed transcripts that do not code for proteins. They affect gene regulation by binding to transcripts and inhibiting their translation to proteins (i.e., post-transcriptional silencing) or by guiding the positioning of nucleosomes along the genome and thereby altering DNA accessibility. Designed by Vinícius Gaio, London, UK.

Figure 2

Factors and environmental confounders influencing epigenetic profiles. The assessment of these factors should be included in the design of a study investigating epigenetic profiles.

Figure 3

PRISMA flow diagram of study selection