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Common rarity in 7 out of 7 ME/CFS patients based on 23andMe results

Hip

Senior Member
Messages
17,824
There are a couple of problems with this result. The first is that rs952061 is located outside of a gene rather than nicely inside of it. So it's in an "intergenic region". Intergenic SNPs aren't directly involved in creating the proteins made by genes.

However, intergenic SNPs can still promote and enhance nearby genes, thereby regulating them. It is also possible that SNPs currently thought to be intergenic are actually part of discovered genes. Hence rs952061 might be on an undiscovered gene, or it might be affecting the nearby MYBPC1.

The other problem is that there's been no apparent research into rs952061. Even though the dbSNP shows a couple boxes for it, there's no links to any research. Searching google scholar and google also bring up nothing for rs952061.

Hence there's no way to be certain that this SNP does anything at all, much less anything relevant to us. Any conclusions are entirely guesswork based on the rarity of our genotypes, our shared disease and symptoms, and the proximity of rs952061 to the MYBPC1 gene.

This is a fantastic project you have set up, Valentijn — this software you designed that analyses 23andme.com genotype data files in search of SNP alleles that are particularly common in ME/CFS patients, but uncommon in the general population.

It is amazing to see that a genuine scientific result has emerged from this project: your discovery that the rs952061 SNP is common in ME/CFS patients, but very uncommon in the healthy population.

It is a shame that this rs952061 SNP that you found in ME/CFS patients is located in the intergenic region of the genome, and is not part of any gene. It would have been great if this SNP were part of a well researched gene, so that we could then try to understand the biochemical ramifications of the mutation. Though as you say, this SNP might affect the nearby gene MYBPC1.

In any case, it is great to see an actual scientific discovery emerge from your project.

I wonder if it is worth contacting Dr Enlander regarding this result? It says in this post that Enlander may pick up where Jonathan Kerr left off with ME/CFS SNP research.

I also wonder whether some other rare SNPs might turn up if a larger set of ME/CFS patients were analyzed (say 200 or so ME/CFS patients).

Another possible extension to this project might be to check to see if there were any particular combinations of SNP mutations present in ME/CFS patients.

For example, it may be that ME/CFS patients have a certain simultaneous set of SNP mutations that are each quite common in healthy controls, but are uncommon to have simultaneously in combination. I don't know if there is any scientific rationale in this, and it is perhaps an odd concept, but this idea crossed my mind.


In terms of how the MYBPC1 gene might relate to ME/CFS: the protein this gene encodes for is myosin binding protein C, and the following presentation indicates that MYBPC1 plays a role in immune function:

Cardiac Myosin Binding Protein-C Prevents Immune Response-Triggered Cardiac Myocyte Death During Inflammation
 

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
To me, this shows how easily initial findings can later turn out to be insignificant. The initial 7/7 seems to be merely a coincidence and I dare say the T allele may turn out to be more common than suspected if a population based dataset was used for a comparison.

That said, we need to keep looking or we will never find anything.
 
Messages
15,786
To me, this shows how easily initial findings can later turn out to be insignificant. The initial 7/7 seems to be merely a coincidence and I dare say the T allele may turn out to be more common than suspected if a population based dataset was used for a comparison.

That said, we need to keep looking or we will never find anything.
Agreed on all accounts. I now have 14 full 23andMe profiles to look at for this data, which makes a very big difference in avoiding false positives. I've also added a similar number of controls, which makes it a lot easier to get a "feel" for how the data looks:
rs952061.jpg


While we still have more T, compared to the controls, it's not much of a difference when seen here with a bigger sample size. Hence I think it's helped quite a bit to get those full profiles, as the negative results are then as clear as the positive results.

I also very much enjoy the enthusiasm, discussions, and learning that results from these investigations - looking into these things has forced my ME brain to learn a helluva lot about something new to me. And hopefully ME/CFS patients will keep contributing their results, so we can keep looking for any commonalities. I also intend to process shared SNPs again soon, since I have a bunch of new rare results to add to the mix, to see if anything new emerges, especially when compared to the controls.
 
Last edited:

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
Agreed on all accounts. I now have 14 full 23andMe profiles to look at for this data, which makes a very big difference in avoiding false positives. I've also added a similar number of controls, which makes it a lot easier to get a "feel" for how the data looks:
View attachment 6327

While we still have more T, compared to the controls, it's not much of a difference when seen here with a bigger sample size. Hence I think it's helped quite a bit to get those full profiles, as the negative results are then as clear as the positive results.

I also very much enjoy the enthusiasm, discussions, and learning that results from these investigations - looking into these things has forced my ME brain to learn a helluva lot about something new to me. And hopefully ME/CFS patients will keep contributing their results, so we can keep looking for any commonalities. I also intend to process shared SNPs again soon, since I have a bunch of new rare results to add to the mix, to see if anything new emerges, especially when compared to the controls.

I think if one compares the percentages its still quite a scientific difference. I think there needs to be about 100 ones with ME canadian defined to compare with equal number of controls so really hope you keep on analysing this as it may be "part" of an answer.