I might have forgotten or missed something, but why zero in on TLR7? If we're working with the idea of X chromosome dosage, there are lots of other genes that aren't fully silenced on the second X. For example TLR8 right next to it. From another paper:
If we're talking about the recent mouse...
This is the TAOK3/SUDS3 region.
The GTEx project shows that variants alter expression differently in different cell types/organs. So I think that's possible.
For example, maybe the ME/CFS variant increases TAOK3 in the liver while the SLE variant decreases TAOK3 in the skin, or even alters the...
I'll note that from my amateur attempt to try to determine if both studies share a causal variant at this locus, it doesn't seem like it's the case that they do.
First of all, when looking only at the region that includes this locus, chr12:118110000-118470000, there are 344 SNPs that are...
Interesting article! If the points in the article are correct, the science is shockingly bad in The Body Keeps the Score.
Some snippets:
From the book which is a rebuttal to the book in question:
That paper refers to a study/dataset from the same author from a year earlier: GCST011096. It has slightly fewer Asian cases, but it looks like the same European sample. So it is based on 8798 cases and 16470 controls from mixed ancestry.
I was able to download this data and plot it. And it...
It doesn't look like it was significant in this study. And the Bentham 2015 paper doesn't mention any locus in this region. It mentions two other loci on chromosome 12, which can be seen if I zoom out really far. The ME/CFS TAOK3 locus is the left red tower. (Not all gene names shown.)
Looking...
Sorry, my plot was probably a bit misleading on this front since it was so zoomed in. It gives quite a different picture if I zoom out to include the full SLE locus (not all genes shown):
Using the Thermal Power of Light to Affect Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Hochecker, Barbara
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and poorly understood multisystem disease with an unclear cause and pathophysiology...
I'm running into an issue with the Sjogren's data because the dataset only has the effect allele for each variant and not the reference allele, but Bigagwas requires both. So I'm not sure I'll be able to test a genetic correlation with this dataset.
I did explore the plots, looking at the...
I'm just surprised that this study only happened five years after the start of the pandemic and seeing long COVID beginning to appear, since it seems fairly straightforward to infect mice then see how their behavior changes after many weeks split by sex.
But it seems like pretty good evidence...
This study looks promising and has downloadable data: https://www.ebi.ac.uk/gwas/studies/GCST012796
Though it's a relatively small sample (585 cases if using just European participants). But I'll try to test the correlation with ME/CFS using this.
The lupus locus on chromosome 1 above is right above TNFSF4 (AKA OX-40 ligand). There are a lot of papers talking about the connection between this gene and lupus, for example:
Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to systemic lupus erythematosus (2013)
Web |...
There's a lot of genes in the area. It might be that the loci relate to totally different genes and their proximity is a coincidence.
Though DNA is a very, very long thing, so it kind of seems unlikely to me to happen to be right next to each other by chance. But possible.
When I previously ran LDSC to test for genetic correlations between DecodeME and all the traits in the UK Biobank, the correlation with lupus didn't work, likely because the sample size in the Biobank was too small.
Recent discussions about lupus made me want to see if I could get it working...
This is really interesting. Looking at the number of patients that have an extra X chromosome helped nail down that the X chromosome was a risk factor for SLE. Here are the two papers it cites for the above:
Klinefelter's syndrome (47,XXY) in male systemic lupus erythematosus patients: Support...
Yes: https://www.gtexportal.org/home/gene/TLR7
The variants listed under "Significant Single-Tissue eQTLs for TLR7" are associated with changes in expression of TLR7.
They're categorized by tissue. There is a chance there are no variants that increase expression in the tissue that matters...
The hypothesis is that the dose of a gene matters for ME/CFS. One way of increasing dose is being female. But you'd expect any other mechanism that increases expression/function of the gene, if such a mechanism exists, to also increase risk. Such as a genetic variant. Maybe even an environmental...
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