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

SOC

Senior Member
Messages
7,849
I think it came to my mind because the top level of my son's depression manifests itself as fatigue. For over a year and a half he had terrible fatigue and I think he might have ended up with CFS if we hadn't finally found out he had the MTHFR 677 gene mutation and the fatigue was relieved by taking methylfolate. It was later that I found out that the fatigue was caused by histamine and that this histamine could cause extreme depression that I got a link in my mind between fatigue and depression. Actually, I think now the depression was caused by the fact that he has been having more histamine during the day than at night and it is messing up his ability to regulate SAMe.
Depression can manifest as fatigue, but fatigue does not equal ME/CFS or even CFS. Fatigue is a symptom of many illnesses. ME/CFS is a complex multisystem disorder including autonomic and immune dysfunction among a number of other problems. Depression is NOT a symptom of ME/CFS. Some people with ME/CFS have reactive depression after having their lives destroyed by this horrific illness, but that's true of most people with severe chronic illness.
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
Im so glad that you are trying to work it out Valentijn. I personally think that one of us who have the disorder is more likely to figure out the answers to this illness then a scientist due to the lack of those studies and funding.

Im right now excited to read of your finding and will try to find out what mine is in a moment. We could end up being the first patient group who ends up solving their own illness. We have results easily in our hands and we have the internet to compare with one another. We actually do have a lot of power to be able to sove our own illness if people work together to do so..
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
From the replies now (removing thou the two who said they werent diagnosed with ME/CFS as I think thats important as anyone who isnt may not have all the proper ruling out of as much as possible). That leaves 36 responses.

Out of those there are 5 TT homo (amazing result if this only occurs normally in 1 out of 100!!), 12 are CT hetero and 19 dont have a mutation.. CC. This needs proper further research!!!! We are getting close to 50% who have a mutation in this gene so I think its highly revelent even without those startling TT results esp when we also know there are lots of misdiagnoses of ME/CFS.

Those who dont have offical ME/CFS diagnoses please say and it would be great if all those of the CC group shared if they have at least CC CFS or not for better analyses of what could be going on.. Out of those who are CC, I think quite a few dont have CC CFS or ME international defined ME. As we all know how important it is to subgroup, it would be great to know how many dont there thou now that Ive had a better look, I know at least several there do fit CC CFS or ME defintions. (I was surprised to see a few with similar ME to me in the CC group).

TT
allyb
Gypsy A
rosie60
Blue
Crux

CT
nandixo
sea
Valentijn
Gypsy A daugher
Clodomir
bel canto
annie likes red
Aileen Kimsie
Helen
Wool Pipi
Taniaaust1

CC
dsdmon
mabelark
adreno
ukxmrv
thinktank
Lucys
Hip
brenda
snow athlete
caledonia
creekee
biophile
wordweaver27
Ruthie24
Alklein
Ema
acer2000
sickofsickness
rawcreamqueen
.......

Can we get a researcher interested in this who could do a study which could be published? Maybe we could draw attention of this to the 23andME company themselves as they do studies and put out their findings. They could be excited if someone put an exciting discovery right down for them to take on and get the full credit for the discovery.
 
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ukxmrv

Senior Member
Messages
4,413
Location
London
Thanks Val for such a great effort. I'm CC (just doubled checked 23 and ME)

My original dx was ME as per Ramsay in the UK. From an outbreak in the mid-80s.

Also meet the criteria for ME/CFS as per the Canadian criteria.
 
Messages
15
I have been diagnosed with CFS/ME just recently although probably suffering from it for almost 10 years after a "flue"....
 
Messages
15,786
@Valentijn
thank you - little star:):):)
of course I have no idea what it means............
CC is the common variant in the general public.

Something I've been working on is compiling a list of the most shared rare SNPs in ME/CFS patients, and looking to see if they trace back to a common gene. Thus far, there are 29 rare SNPs shared by at least 3 (out of 16) ME/CFS patients in the homozygous form which are on genes that either affect AKT1 or affect genes which affect AKT1.

That's after removing likely false positives, based on prevalence in the 7 controls (people who certainly do not have ME/CFS/CF or even fatigue or pain) . Positive results shared by only 3 patients were also removed if 2 of those patients were relatives, to err on the side of caution.

So that produces the following results (C1-C7 are controls, P1-P16 are ME/CFS patients):
cluster1.gif


The average number of rare homozygous mutations on these genes is 6.9 for patients and 0.4 for controls.

I only had partial data (rare homozygous mutations) for P10-P16, hence, hence the general lack of heterozygous mutations shown for them. Patient P5, who has a low number of shared rare homozygous mutations sounds like a pretty typical moderate or worse ME/CFS patient, as defined by CCC/ICC, and without any other obvious explanation for her symptoms. So it would seem that there's still a problem with either not detecting all of the relevant SNPs, or the entire theory is wrong. But the other low scoring patient, P12, doesn't have typical CCC/ICC ME/CFS symptoms, though he does have some shared issues.

Anyhow, this might be an indication that instead of a specific SNP or gene being relevant, their relationship to another gene is the significant factor. Hence AKT1 might be causing a similar set of problems in different people, based on mutations in different genes which are having a fairly direct impact on AKT1. So even though you don't have the rare version of that one SNP, a combination of other SNPs might be having the same impact.

If anyone wants to use 23andMe to look up their genotypes for these SNPs, here's a text list including the rare allele:
rs13118884 A
rs10457667 A
rs1338457 A
rs6799780 G
rs11791618 C
rs10735443 A
rs1946282 G
rs6816809 A
rs476951 A
rs11057369 A
rs4720309 A
rs4279979 G
rs17762542 G
rs5965630 A
rs6786329 C
rs2979001 T
rs2221513 G
rs952061 T
rs36880 C
rs137954 G
rs17780664 G
rs17133109 A
rs17321293 C
rs2417266 C
rs2139567 T
rs13133587 T
rs7912364 A
rs11907065 C
rs12732188 A

If anyone wants to give me their data for these SNPs, and hasn't already given me their full 23andMe results or rare homozygous results, please post here or send them to me in a private message/conversation if you want to keep them anonymous. It also helps very much if you specify which definition of ME/CFS you meet the criteria of. But full 23andMe results or homozygous rare results are even more useful, if you feel comfortable sharing them.
 
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leela

Senior Member
Messages
3,290
Well, Val, whatever it is, there is *clearly* something going on here.
Even though a small sample group, the obvious weightedness in the patient group compared to controls
could be a real selling point/motivator towards getting serious science pointed at this illness.

Bowing deeply to you for doing this, with total certainty that this will lead to a beneficial outcome.