Results of the largest ever study into the Genetics of me/cfs.

[andyguitar]

Once analysed this research could help in finding treatments and identifying subgroups/types.

 

[andyguitar]

Phew 46 pages of info! So far....1)None of the genes relate to depression/anxiety. 2) Three most likely genes produce proteins that respond to infection. 3) Me/cfs is partly caused by genes related to the immune and nervous system. So the shrinks can go fu*k themselves.

 

[Viala]

That's a huge study, 21k people with ME vs almost 260k controls. Wow.
Genetic testing could help in getting a diagnosis then.

The good news is that only 17% is getting worse, I thought it will be worse. The majority is fluctuating. Then about 63% started with infection, also thought this number will be higher. No gene differences explaining why women get sick more often, that's a bit surprising.

 

[bad1080]

21k people with ME vs almost 260k controls

shouldn't they be paired (age, gender and amount) as close to 1:1 as possible?

 

[andyguitar]

No gene differences explaining why women get sick more often, that's a bit surprising.

Yes it is. First thoughts from me about that are perhaps women have a greater exposure to the triggers that start me/cfs?

 

[Rufous McKinney]

Yes it is. First thoughts from me about that are perhaps women have a greater exposure to the triggers that start me/cfs?

I asked the nebulous Internets, and it pretty much said:

Female hormones and female Immune systems differ. Also there is potential for differing social roles and early stress, which could be a trigger.

So the same gene may end up expressing or operating differently, depending upon which sex you are.

This paper may have some background that might be helpful.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8228628/

Biomedicines
. 2021 Jun 8;9(6):652. doi: 10.3390/biomedicines9060652

Gender Specific Differences in Disease Susceptibility: The Role of Epigenetics​

Lucia Migliore 1,2,*, Vanessa Nicolì 1, Andrea Stoccoro 1

 

[andyguitar]

This is one of the genes in question BTN 2A2, look what it says about CD4/CD8 T Cells......

 

[Gala]

I found this very interesting: The MAGMA analysis showed that the genes associated with ME/CFS are significantly overexpressed in 13 brain regions, especially in the frontal cortex, basal ganglia, and hypothalamus, implicating the central nervous system in the disease. No significant associations were found in other tissues after statistical correction.

 

[Gala]

Potential Role of the 8 Genes in ME/CFS (DecodeME 2025)

- RABGAP1L: Involved in innate immunity against bacterial and viral infections. Dysregulation may contribute to post-infectious onset of ME/CFS.

- BTN2A2: Regulates immune tolerance and T-cell co-stimulation. Its dysfunction may underlie persistent immune dysregulation observed in ME/CFS.

- FBXL4: Crucial for mitochondrial function and energy production. Variants may impair oxidative phosphorylation, contributing to fatigue.

- SUDS3: Participates in transcriptional repression and epigenetic regulation. May play a role in maintaining a hypo-metabolic or immune-altered state.

- OLFM4: Expressed in immune and epithelial cells, it may modulate chronic inflammation and neuroimmune signaling in ME/CFS.

- CCPG1: Key regulator of endoplasmic reticulum (ER) stress and autophagy. Chronic ER stress may contribute to cellular dysfunction in ME/CFS.

- CA10: Involved in neuronal signaling and pH regulation in the brain. Dysfunction may relate to cognitive symptoms and brain fog.

- ARHGEF2 / CSE1LARHGEF2: Affects neuroinflammation via Rho GTPase signaling. CSE1L modulates nucleocytoplasmic transport and gene expression. Both may affect neuroimmune communication.

 

[southwestforests]

No gene differences explaining why women get sick more often, that's a bit surprising.

Yes it is. First thoughts from me about that are perhaps women have a greater exposure to the triggers that start me/cfs?

Brings to mind that the first person I ever heard of having ME/CFS in early 1980s was my Dad, who at the time was active duty US Navy cold war and Vietnam veteran.

1960s and 1970s and 1980s Navy ships, and the Vietnam war, and the Saudi Arabia Navy, weren't exactly things it was primarily women getting exposed to.

 

[Violeta]

The only Tier 1 gene in the chr17q22 interval was CA10, whose genetic variation could begin to explain the pain experienced by over 86% of DecodeME’s ME/CFS cases. The CA10 protein inhibits the addition of heparan sulfate glycosaminoglycan to presynaptic neurexins.

Not in the paper:
Presynaptic neurexins are crucial cell adhesion molecules in the brain, playing a key role in synapse formation and function. They are located on the presynaptic side of synapses and interact with various postsynaptic proteins, influencing synaptic transmission and plasticity. Mutations in neurexin genes are linked to neuropsychiatric disorders like autism and schizophrenia.

 

[Treeman]

Hi, I was a participant in the study, but don’t get individual feedback.

I know I have a mutation on NFKB2 which they believe affects the immune system. The document is too long for me to read, was NFKB2 mentioned? Thanks.

 

[Viala]

Yes it is. First thoughts from me about that are perhaps women have a greater exposure to the triggers that start me/cfs?

That would support stronger nurture than nature influence. Women in general get sick more often with autoimmune diseases and ME/CFS might be a part of this cluster. I guess we won't know for sure, it still may be anything from different upbringing of girls to naturally higher estrogen levels.

 

[joshualevy]

shouldn't they be paired (age, gender and amount) as close to 1:1 as possible?

No, unless the experimental design explicitly calls for a paired control group.
Most studies do no use a paired control group, instead they publish a statistical summery of the treated group and the control group which should show that they are statistically similar. Paired controls are a less common method. Still works, just not as common. Also, there is nothing magic about a 1:1 treated to control ratio. I've seen plenty of studies with N:1 and 1:N. The real issue is: how hard/expensive is it to enroll more people. If it is easy and cheap, no reason not too. I think that was the case here, because they were just using stored samples.

 

[Violeta]

Hi, I was a participant in the study, but don’t get individual feedback.

I know I have a mutation on NFKB2 which they believe affects the immune system. The document is too long for me to read, was NFKB2 mentioned? Thanks.

I haven't seen it in there so far. These are the most important ones, but I don't know if there are others.

 

[Violeta]

Hi, I was a participant in the study, but don’t get individual feedback.

I know I have a mutation on NFKB2 which they believe affects the immune system. The document is too long for me to read, was NFKB2 mentioned? Thanks.

Amatica is doing genetic testing. NFKB2 is one of the genes they are looking at.

 

[sb4]

How would one go about checking if they have defective variants of the RABGAP1L gene for example.

I've put RABGAP1L into my23andme and it comes up with dozens of RS Markers.

The study doesn't seem to be using RS Markers.

I wonder if it's looking at sequences not on my23andme or I just don't know what to look for.

 

[I am sick]

I haven't seen it in there so far. These are the most important ones, but I don't know if there are others.
View attachment 56061

I agree with my symptons I just cant read for hours either , I loose interest real quick.

 

[I am sick]

That would support stronger nurture than nature influence. Women in general get sick more often with autoimmune diseases and ME/CFS might be a part of this cluster. I guess we won't know for sure, it still may be anything from different upbringing of girls to naturally higher estrogen levels.

Being male I can say females are very strong and tuff ! Mentally and physically.
I don't think the number is accurate
Or it is wrong due to other unknown Varibles.
Everyone is searching and researching
And none of us know what to check at this point?
But every bit of data helps for sure and we need it to move forward.

 

[Rufous McKinney]

The document is too long for me to read, was NFKB2 mentioned? Thanks.

you could try doing a FIND search (perhaps)...that exists under the editing tab on my Mac.