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Genetic risk factors for ME/CFS identified using combinatorial analysis

SWAlexander

Senior Member
Messages
2,018
Published: 14 December 2022
Abstract
Background
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease that lacks known pathogenesis, distinctive diagnostic criteria, and effective treatment options. Understanding the genetic (and other) risk factors associated with the disease would begin to help to alleviate some of these issues for patients.
Methods
We applied both GWAS and the PrecisionLife combinatorial analytics platform to analyze ME/CFS cohorts from UK Biobank, including the Pain Questionnaire cohort, in a case–control design with 1000 cycles of fully random permutation. Results from this study were supported by a series of replication and cohort comparison experiments, including use of disjoint Verbal Interview CFS, post-viral fatigue syndrome and fibromyalgia cohorts also derived from UK Biobank, and compared results for overlap and reproducibility.
Results
Combinatorial analysis revealed 199 SNPs mapping to 14 genes that were significantly associated with 91% of the cases in the ME/CFS population. These SNPs were found to stratify by shared cases into 15 clusters (communities) made up of 84 high-order combinations of between 3 and 5 SNPs. p-values for these communities range from 2.3 × 10–10 to 1.6 × 10–72. Many of the genes identified are linked to the key cellular mechanisms hypothesized to underpin ME/CFS, including vulnerabilities to stress and/or infection, mitochondrial dysfunction, sleep disturbance and autoimmune development. We identified 3 of the critical SNPs replicated in the post-viral fatigue syndrome cohort and 2 SNPs replicated in the fibromyalgia cohort. We also noted similarities with genes associated with multiple sclerosis and long COVID, which share some symptoms and potentially a viral infection trigger with ME/CFS.
Conclusions
This study provides the first detailed genetic insights into the pathophysiological mechanisms underpinning ME/CFS and offers new approaches for better diagnosis and treatment of patients.

To read the very long paper: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03815-8

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SWAlexander

Senior Member
Messages
2,018
Did anybody read: The Prusty Files: HHV-6 Found in the Brains of ME/CFS Patients.
https://www.healthrising.org/blog/2022/12/15/prusty-hhv-6-brains-chronic-fatigue-syndrome/


That opens up another can of worms, at least for me since the test from last year confirmed HHV-6.
I had it already as a child.
I wonder what genetic defect HHV-6 will be discovered. Have not found any clear evidence (yet).


At the same time, I try to analyze/understand Polio Research in relation to ME/CFS.
Dendritic Cells and Macrophages Are Productively Infected by Poliovirus

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC538697/
 
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SWAlexander

Senior Member
Messages
2,018
What test did you do to find your genes in the first place?

I have 2 tests with 23andme.com. The first one was in 2010 when they used V3 and the second 2021 when they updated to V5.

Which ones do you have and do you think based on your symptoms, they align with what their study is saying?
I will post an example when I´m finished checking. It´s manual checking and very tedious and time consuming.
 
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