Much-needed data on the genetics of #longCOVID in a new preprint by @23andMeResearch

SWAlexander

SWAlexander

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Thank you BrightCandle

rs9273363: related to Typ 1 diabetic and 3 inflammatory diseases

rs8176719: related illnesses https://www.snpedia.com/index.php/Rs8176719

rs2080090: partial explanation: https://www.ebi.ac.uk/gwas/search?query=BPTF

same with: rs7502307

See also:

Multi-ancestry GWAS of Long COVID identifies‬ ‭immune-related loci and etiological links to chronic fatigue‬ syndrome, fibromyalgia and depression‬ ‭​

https://www.medrxiv.org/content/10.1101/2024.10.07.24315052v1​


Related:

Langerhans Cells: Immune Function, Genetic Markers, and Pathology
https://swaresearch.blogspot.com/2024/10/langerhans-cells-immune-function.html​

 
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cfs since 1998

cfs since 1998

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SWAlexander said:
Thank you BrightCandle

rs9273363: related to Typ 1 diabetic and 3 inflammatory diseases
Click to expand...
rs9273363 was the strongest association.

Interesting the T1 diabetes effect is opposite the long COVID effect.

The 'C' allele of rs9273363 is protective against T1 diabetes but increases your risk of long COVID 6%, with a p-value of 0.0000000000379.

I have the 'C' allele from both parents.

I didn't get Long COVID when I had it (though I had been vaccinated) but I do have post-EBV CFS.
 
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W

Wishful

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I haven't looked at the article, so I don't know what sort of numbers are involved, but my first thought was that if you look at the night sky (or any random data), you'll find what appear to be meaningful patterns, but really aren't.
 
cfs since 1998

cfs since 1998

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Messages
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Here is more information about the most highly associated polymorphism, rs9273363.

The rs9273363 polymorphism spans across the HLA-DQA1 and HLA-DQB1 genes.

HLA (human leukocyte antigen) genes have been identified as being associated with ME/CFS by at least four independent research groups in the UK, Italy, Israel, and Norway (Smith 2005, Carlo-Stella 2009, Ortega-Hernanzes 2009, Hajdarevic 2021).

While the specific risk alleles were not identical across the four studies, it is common for autoimmune diseases to have different risk alleles in different populations (ref).

The HLA-DQB1 gene specifically has been associated with ME/CFS by the Norweigan group. It is "a gene important for antigen-presentation to T cells and known to harbor alleles providing the largest risk for well–established autoimmune diseases" (Hajdarevic 2021).

In Norway, patients carrying the associated HLA risk alleles in the HLA-DQB1 and HLA-C genes were more likely to respond to cyclophosphamide.
 
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sometexan84

sometexan84

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cfs since 1998 said:
Here is more information about the most highly associated polymorphism, rs9273363.

The rs9273363 polymorphism spans across the HLA-DQA1 and HLA-DQB1 genes.
Click to expand...
Pretty sure I have the rs9273363 SNP, as I have DQA1*03:01 and DQB1*03:02 alleles. (So the DQ8 serotype)

I also have DRB1*04:01 (So the DR4 serotype)

And thus I also have the combined HLA-DR4-DQ8 haplotype.

Here's some of my personal notes on this, showing diseases I'm higher risk for based on my HLA risk alleles w/ link references to the studies I found. This is only showing the alleles I mentioned above that I myself have.

DQ8 (DQA1*03:01 - DQB1*03:02) Freq: 9.62% in Caucasian Americans

Type 1 Diabetes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678473/
Celiac disease
https://www.verywellhealth.com/hla-dq8-one-of-the-main-celiac-disease-genes-562571

DR4 (DRB1*04:01)
Rheumatoid arthritis
Obstructive hypertrophic cardiomyopathy
IgA nephropathy - P=0.005 (glycan, Endothelial cell, mesangial cell, dextran, GBM)
https://en.wikipedia.org/wiki/HLA-DR4
Polymyalgia rheumatica (ferritin, intermediate filament, mitochondrial) (P = 0.0001)
https://pubmed.ncbi.nlm.nih.gov/8147928/
Pemphigus foliaceus (desmoglein-1) (P < 0.02)
https://onlinelibrary.wiley.com/doi/10.1111/j.1399-0039.1981.tb00689.x
'shared syndrome'-systemic sclerosis/rheumatoid arthritis (numbers don’t look significant)
https://academic.oup.com/rheumatology/article/46/6/989/2899480
Hashimoto’s - OR=1.98
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647156/
MOG (IgM) antibodies in MS
https://pubmed.ncbi.nlm.nih.gov/12458053/

DR4–DQB1*0302
Islet antigen 2 [IA–2]
https://link.springer.com/article/10.1007/s00125-005-1844-x

DR4-DQ8 (DRB1*04:01 - DQA1*03:01 - DQB1*03:02)
Juvenile diabetes
Coeliac disease
Rheumatoid arthritis
https://en.wikipedia.org/wiki/HLA-DR4


The list above is only a sample of all my HLA risk alleles and the notes I have. But overall, there's a strong pattern of persistent-enterovirus related diseases.
 
sometexan84

sometexan84

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Trying to find how rs9273363 could be involved in allowing a persistent SARS-CoV-2 or Enterovirus infection.

I see rs9273363 involves "protein tyrosine phosphatase receptor kappa (PTPRK)". I couldn't find anything on PTPRK and enterovirus. But I do see that PTPRK dephosphorylates EGFR (epidermal growth factor receptor), which is interesting. So PTPRK is a major negative regulator of EGFR.

EGFR is used, induced, and is even required for many viruses to continue spreading to other cells.

SARS-CoV-2 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141239/
Influenza, Cytomegalovirus, Hepatitis, Zika, EBV - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785968/

Summary:

rs9273363 may be an SNP that makes it easier for viruses to replicate, as dysfunctional PTP allows for uncontrolled activation of EGFR, which appears to aid in NON-LYTIC viral spread.

Also, EGFR activation suppresses interferon response. So that could play a role as well.
 
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