McGowan – American ME and CFS Society

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an example of a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as with specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, the association between DNA methylation and genetic background in relation to the ME/CFS is currently unknown.

In this study we explored this association by characterizing the genomic (~4.3 million SNPs) and epigenomic (~480 thousand CpG loci) variability between populations of ME/CFS patients and healthy controls. We found significant associations of methylation states in T-lymphocytes at several CpG loci and regions with ME/CFS phenotype. These methylation anomalies are in close proximity to genes involved with immune function and cellular metabolism.

Finally, we found significant correlations of genotypes with methylation phenotypes associated with ME/CFS. The findings from this study highlight the role of epigenetic and genetic interactions in complex diseases, and suggest several genetic and epigenetic elements potentially involved in the mechanisms of disease in ME/CFS.

Source: Santiago Herrera, Wilfred C. de Vega, David Ashbrook, Suzanne D. Vernon, Patrick O. McGowan. Genome-Epigenome Interactions Associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. bioRxiv preprint first posted online Dec. 22, 2017; doi: http://dx.doi.org/10.1101/237958. (Full article)

By their very nature, complex disease phenotypes are characterized by the dysregulation of multiple physiological systems, polygenic origins and various environmental triggers that result in patient populations with heterogeneous symptom profiles. Less than 10% of the heritability of complex phenotypes and disease traits are due to genetic variation, indicating that other factors play major roles in disease onset and progression [1]. Epigenetic modifications may partly account for this ‘missing heritability’ [2] through mechanisms that regulate transcriptional potential. These mechanisms appear to be, at least to some extent, responsive to environmental exposures or treatments. An improved understanding of the pathophysiology underlying complex phenotypes and new diagnostic tools can help refine and update classification criteria reliant on nonspecific or self-reported symptoms. Consequently, unraveling complex phenotypes depends to a large extent upon an ability to discriminate what are likely many distinct conditions. We and others have argued that epigenetic investigations integrate multiple levels of information (genetic, stochastic and environmental) to enable a better understanding of the dimensions of illness underlying complex phenotypes [2,3]. Here, we turn to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to illustrate progress and future directions in this regard.

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Source: de Vega WC, McGowan PO. The epigenetic landscape of myalgic encephalomyelitis/chronic fatigue syndrome: deciphering complex phenotypes. Epigenomics. 2017 Nov;9(11):1337-1340. doi: 10.2217/epi-2017-0106. Epub 2017 Oct 18. https://www.futuremedicine.com/doi/full/10.2217/epi-2017-0106 (Full article)