Integration of DNA Methylation & Health Scores Identifies Subtypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract

Aim: To identify subtypes in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) based on DNA methylation profiles and health scores. Methods: DNA methylome profiles in immune cells were integrated with symptomatology from 70 women with ME/CFS using similarity network fusion to identify subtypes. Results: We discovered four ME/CFS subtypes associated with DNA methylation modifications in 1939 CpG sites, three RAND-36 categories and five DePaul Symptom Questionnaire measures. Methylation patterns of immune response genes and differences in physical functioning and postexertional malaise differentiated the subtypes. Conclusion: ME/CFS subtypes are associated with specific DNA methylation differences and health symptomatology and provide additional evidence of the potential relevance of metabolic and immune differences in ME/CFS with respect to specific symptoms.

Keywords::

• CFS
• chronic fatigue syndrome
• clinical subtyping
• complex disease
• DNA methylation
• epigenetics
• health survey
• myalgic encephalomyelitis
• similarity network fusion
• symptom heterogeneity

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: https://www.tandfonline.com/doi/suppl/10.2217/epi-2017-0150

Financial & competing interests disclosure

This work was funded by startup funds from the University of Toronto and an operating grant from the Solve ME/CFS Initiative awarded to P O McGowan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study adheres to the human experimentation guidelines according to the Helsinki Declaration of 1975. The collection and analysis of patient samples and information by the SolveCFS BioBank were approved by the Genetic Alliance ethics review board (IRB # IORG0003358) and the University of Toronto (IRB #27391). Both review boards also approved procedures for obtaining written informed consent from all participants in the study. Two copies of the consent form were signed: one copy is under secure storage at the SolveCFS Biobank and the other copy was provided to the participants.

Data deposition

The datasets supporting the conclusions of this article are available in the Gene Expression Omnibus repository under the accession numbers GSE93266 (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE93266) and GSE102504 (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102504).

Additional information

Funding

This work was funded by startup funds from the University of Toronto and an operating grant from the Solve ME/CFS Initiative awarded to P O McGowan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.