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ME/CFS Variant Spreadsheet with Frequencies, CADD scores, Variant Effect Prediction, etc (Citizen Science)

kday

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@kday, I believe everyone should be GG for that one. OpenSNP is suggesting that 23andMe apparently had a number of no-calls for that SNP, so I think that may be why the allele frequency for the G allele (i.e., the normal allele) in the spreadsheet has the appearance of being so low for the ME/CFS patients.
The spreadsheet ignores and does not tally no calls, so that's not the case. :)

edit: Spoke too soon. It is tallying the no calls. Argh! I thought I got that right! I'll have to correct.
 
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kday

Senior Member
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334
@kday, I believe everyone should be GG for that one. OpenSNP is suggesting that 23andMe apparently had a number of no-calls for that SNP, so I think that may be why the allele frequency for the G allele (i.e., the normal allele) in the spreadsheet has the appearance of being so low for the ME/CFS patients.
Bug fixed.

@Moof you might want to take a look at those 3 variants again.
 

nandixon

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@kday, The openSNP sample size for the ME/CFS patients is probably much too small to be able to make any statistically meaningful associations for genetic analysis purposes. There is however another ME/CFS dataset you might be able to use:

The data that Klimas gathered for the study of this thread:
https://forums.phoenixrising.me/thr...-me-cfs-a-pilot-study-perez-et-al-2019.76400/

is a perfect opportunity for you to apply your skills, if you're able to. That data was completely incorrectly analyzed by Klimas' students and will end up being a huge waste of potentially very valuable data unless it's re-analyzed.

I'm wondering if you might be able to obtain that data from Klimas by offering to do a proper analysis similar to what you're doing now?
 

kday

Senior Member
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@kday, The openSNP sample size for the ME/CFS patients is probably much too small to be able to make any statistically meaningful associations for genetic analysis purposes. There is however another ME/CFS dataset you might be able to use:

The data that Klimas gathered for the study of this thread:
https://forums.phoenixrising.me/thr...-me-cfs-a-pilot-study-perez-et-al-2019.76400/

is a perfect opportunity for you to apply your skills, if you're able to. That data was completely incorrectly analyzed by Klimas' students and will end up being a huge waste of potentially very valuable data unless it's re-analyzed.

I'm wondering if you might be able to obtain that data from Klimas by offering to do a proper analysis similar to what you're doing now?
Factoring in processing time, I could make a table like this in probably an hour or two if I had the data....

I just have to dump those genomes in a database and run a query. It would actually be pretty simple.

That said, I know 25 (or less) is a small sample size. But I do believe I have obtained some meaningful data and insights. The MMP26 region is intriguing. I assume it should hold up with a larger sample size.
 
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kday

Senior Member
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I found this about olfactory receptor pseudogenes. Please read my post about the increase in frequency of these pseudogenes and MMP26 on page 1.

I wonder if these increases in frequency could be causing the hyperosmia and Idiopathic Environmental Intolerance (IEI/MCS) in ME/CFS. What if these pseudogenes are increasing our serotonin (enough increase could create an anxiety-like state), altering our enteric nervous system function and gut motility, and disrupting Ca2+ homeostasis (think NK Cell dysfunction)?

There isn't enough scientific literature to draw any conclusions, but it's in interesting concept to think about.
In 2007, Braun et al. found expression of 4 ORs: OR5D18 (OR73), OR1A1 (hOR17-7/11), OR1G1 (hOR17-209), OR1E3 (hOR17-219) in microdissected human mucosal enterochromaffin cells and in a cell line derived from human enterochromaffin cells. Their studies revealed that the OR activation by the identified odorants cause Ca 2+ influx, elevation of intracellular free Ca 2+ levels, and, consequently, serotonin release, which stimulates the submucosal sensory branch of the enteric nervous system and, via inter- and motor neurons, control gut motility and chloride secretion by enterocytes. The odorant ligands of the identified ORs, OR1G1 and OR1E3, had already been deorphanized by Matarazzo et al. (2005) but Braun et al. were the first ones reporting agonists for the OR5D18 and OR1A1. They reported that OR1G1 is activated by thymol, geraniol, β-ionone, isoamyl acetate, and acetophenone, OR5D18 is activated by eugenol, OR1A1 is activated by geraniol, bourgeonal, and helional and OR1D2 is activated by bourgeonal ( Braun et al. 2007 ).
Unravelling the Olfactory Sense: From the Gene to Odor Perception
 
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kday

Senior Member
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I made a new spreadsheet with 30 genomes. 23andMe, Ancestry, and FT-DNA, which should add a little more statistical relevance. I haven't update the spreadsheet with the new information yet as it's a bit tricky.

Interesting, in both spreadheets, there is variant that is 16x more prevalent than the general population in the PARK7 gene. The frequency in the general population is about 0.85% (so relatively rare). But in ME/CFS the frequency is 13.89%. So while only a fraction of patients have this particular SNP, it's a huge increase in frequency arguing that it may play a role in susceptibility if the results are not chance. It could also mean that people in the early stages of other neurodegenerative diseases are being misdiagnosed with ME/CFS.

Variants in PARK7 has been associated with Parkinsons's (with the phenotype reminiscent of that reported in Guam). In terms of this gene and chemical interactions, it is associated increased oxidative stress from the agricultural chemicals paraquat and rotenone.

This variant (rs11548937) has a high incidence of no-calls in OpenSNP, but it is a real variant, and no-calls aren't counted when making the spreadsheet.

PARK7 is currently tied with a variant in EFCAB13 (rs78865644) which I currently know nothing about other than it's involved in calcium ion binding. No other variants come close to 16x increase in frequency.

Looking at myself and my wife (she is functionally recovered), we don't have these variants. But that's to be expected since the frequency is only 13.89% in ME/CFS genomes. And I looked at my entire PARK7 gene and have no predicted damaging SNPs in the entire gene either. So perhaps this variant is a major risk factor for some cases, but not others.

What's a little baffling is that this is a synonymous variant. Meaning you wouldn't normally expect it to cause issues. So I looked to see if it was in linkage disequilibrium with any other variant in the genome and I couldn't find any. In other words, I can't find any evidence that this variant is "linked" to another variant in the genome.

Sources:
https://www.omim.org/entry/606324
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/park7
https://ldlink.nci.nih.gov/
 
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