Changes in the Epigenetic Landscape of ME/CFS Reflect Systemic Dysfunctions; Helliwell, Thesis 2019, paper 2020

Great. Thank you for finding.

There have been already quite some studies on epigenetics as well.

I think epigenetical changes could be not forced but helped: under good circumstances.

There is also an acetylation of genes (as well of proteins).

 

I downloaded the 210MB file containing 201 pages. Most of it is double Dutch to me.

There were 10 patients and 10 controls, 5 male and 5 female of each. Glancing through the very detailed report and looking at the tables I think the study really needs a much larger sample as differences reported could just be random.

To get useful data with a small sample a project is described that is underway where they will look at individual patient data over time along with relapse/partial recovery symptom reporting where the patient would be their own control.

There might be some useful data in the thesis if it was analysed against individual patient symptoms and clinical testing data. For example the report did have 2 hypermethalated data points that might indicate "Primary Immunodeficiency" - from the table on P148.

Reading it made me wonder what is happening with the Lights large NIH study "Novel Gene Variants In ME/CFS And Fibromyalgia". That study has been very quiet for a while now.

 

This team has previously said that they're aware their cohort is rather small (lack of funding) but that they believe they can still get worthwhile data from it by using methods employed by rare diseases research where you by definition only have a handful of patients. I don't know what those methods are. Maybe what you're describing, an individual being their own control over a long period of time?

 

Merged thread

Changes in the Epigenetic Landscape of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Reflect Systemic Dysfunctions;Helliwell July 2020

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153667

 

I take it this study is one looks at which genes are activated at any given time so you can work out where things aren't working properly.

 

Over my head, but I guess it's related to the thesis in this thread. Looks like the data is being shared in various formats.
https://www.s4me.info/threads/an-ep...ue-syndrome-2019-helliwell-m-sc-thesis.15521/

 

I can't conclude much from this. The study overall is reasonably well conducted and written with a variety of visualisations and analyses.

But none of the findings tie in well with other studies. The discussion is weaker than the rest of the article, the sections on HPA axis in particular read like pandering to a colleague, with a lacking of depth or a critical view of prior studies which potentially contradict the hypothesis. The link between the results of this study and HPA axis dysfunction based hypotheses are particularly weak. The one specific link mentioned was Mitochondrial uncoupling protein 2 hypermethylation (which lowers gene expression) and a study that found that HPA axis stimulation leads to increased UCP2 expression. UCP2 could simply be downregulated in patients due to activity patterns or other metabolic reasons. The reason why HPA axis stimlation leads to increased UCP2 is simply that it is a feed-forward stimulatory process.

The only prior mention of UCP2 in CFS or ME research is an aside in this narrative review by Gerwin Morris et al. https://www.sciencedirect.com/science/article/abs/pii/S1043661819308011