Extract SNPs from 23andme data to yasko/nutrigenomics notation

greenshots · Mar 29, 2012

The AHCY is where homocysteine is activated, when its not working, homocysteine levels are lower and it takes the strain off any CBS defects present (which I think you have?). This means, you may not see the same problems on lab tests with CBS defects (high taurine, ammonia may be a little lower, homocysteine could be normal or high normal despite MTHFR C677T, etc.). SAMe is not warranted here but for the record, I have a double CBS 699t and double AHCY and take SAMe. However, I am a COMT -/- so I can tolerate a BUCKET load of these methyl groups. That's about what I know there, sorry I don't have more for you.

Angela

hixxy82 said:
I'm trying to get my head around the significance of AHCY mutations as I have 1 homozygous and 2 heterozygous! The heartfixer description is really lousy for this mutation.

Is anyone able to confirm if the consequence of AHCY mutations is poor recycling of S-adenosylhomocysteine back to homocysteine resulting in excess SAH and less homocysteine for production of methionine and SAMe?

I suspect there may be a mistake on the heartfixer website the following:

"S-Adenosyl Methionine (SAMe), the key methyl donor generated from methionine, is metabolized in to S-Adenosyl Methionine"

is supposed to be:

"S-Adenosyl Methionine (SAMe), the key methyl donor generated from methionine, is metabolized in to S-Adenosyl Homocysteine"

as it doesn't make sense to metabolize SAMe to SAMe....

Is it also satisfactory to assume that all MTR mutations caused excessive methylb12 degredation and all MTRR mutations result in poor synthesis of methylb12 and this is why heartfixer is grouping them all together?

There's only information out there on a couple of these mutations, not all.

froufox · Mar 30, 2012

Thanks Angela :Retro smile:

greenshots said:
Except for the MTR & CBS, those are up regulations. This is why genetics is so crazy & convoluted that you can get lost in the mix.
Its enough to make you crazy. I agree with Nanonug, seems like the MTHFR A1298C would be normal since its working but the C677T would be +/- and only partially working, which is why they say its moderately working.

Angela

hixxy · Mar 30, 2012

Thanks greenshots. You're a machine! I have suffered from a very severe intolerance of B6 that worsens my brain overstimulating. A lot of my neurological problems started over night with b6 for pyroluria. The funny thing is that I have 3 AHCY mutations one of them homozygous. Shouldn't this almost negate the affect of the CBS? Maybe I should look somewhere else for my B6 problem..... Maybe I have a GAD enzyme problem, but why on earth would it suddenly trigger off like that with B6 supplementation.

I suspected when I ordered the 23andme test that my results wouldn't be very nice, but I truely wish I hadn't got 2 homozygous COMTs! I suspected I would get at least one of these before the results came back. Can't I trade someone???

With the presence of the AHCY mutations, do I still need to treat my CBS? Does anyone here actually test their urine sulfite/sulfate? Maybe I can just bypass this and go onto treating the MT prefixed mutations. Just try muscle my way through it

Do you know what I think?? I think all this genetics talk and information needs a wiki. Heartfixer is good for a reference of some stuff, but is static and unchanging since 2008. That's a looong time ago for this kind of thing. Surely there should be some progress being made.

hixxy

nanonug · Mar 30, 2012

hixxy82 said:
With the presence of the AHCY mutations, do I still need to treat my CBS? Maybe I can just bypass this and go onto treating the MT prefixed mutations. Just try muscle my way through it

Did you actually have your homocysteine levels checked? With your mutations, one would expect it to be somewhat low.

Based on richvank open label study, it appears that "muscling through" could actually work. However, at some point, it would probably be wise to actually measure methylation metabolites and see what is going on.

hixxy82 said:
I think all this genetics talk and information needs a wiki.

Agreed!

hixxy · Mar 31, 2012

Last time homocysteine was checked it was normal. Hasn't been done since start of last year and I was going through major wasting away / malnutrition at the time, so logically you would think with more protein absorption the homocysteine would rise??

Shame the wiki pages here on phoenixrising aren't very wiki-ish!

hixxy

hixxy · Mar 31, 2012

I just thought of something I heaven't seen mentioned about the MTHFR and MTRR mutations. Theoretically couldn't these also cause excess methyl groups to be floating around on top of the other already known COMT, VDR mutations that cause excess methyl groups?

When these enzymes are working optimally they will be using up methyl groups to methylated folate and b12.

hixxy · Apr 1, 2012

In my boredom I created a little tool to interpret 23andMe raw data over to Yasko style notation. It scans through the raw data file looking for SNPs based on a definitions file and does the interpretation. Would be nice to have more SNPs in the definitions file though !

http://www.hixxy.org/23andMe/

Certainly beats doing it manually. There's a sample 23andMe raw data file there as well for someone who hasn't done the 23andMe test that wants to test it.

nanonug · Apr 1, 2012

hixxy82 said:
I just thought of something I heaven't seen mentioned about the MTHFR and MTRR mutations. Theoretically couldn't these also cause excess methyl groups to be floating around on top of the other already known COMT, VDR mutations that cause excess methyl groups? When these enzymes are working optimally they will be using up methyl groups to methylated folate and b12.

MTHFR is inhibited by SAMe. I have seen speculation about the A1298C mutation causing this inhibition mechanism to break down. However, I haven't taken the time to (dis)confirm this.

nanonug · Apr 1, 2012

hixxy82 said:
In my boredom I created a little tool to interpret 23andMe raw data over to Yasko style notation. It scans through the raw data file looking for SNPs based on a definitions file and does the interpretation. Would be nice to have more SNPs in the definitions file though !

http://www.hixxy.org/23andMe/

Certainly beats doing it manually. There's a sample 23andMe raw data file there as well for someone who hasn't done the 23andMe test that wants to test it.

Very nice!

By the way, I have serious concerns about the VDR interpretation on the famous spreadsheet. I even created a thread specifically for this purpose: VDR gene polymosphisms: allelic interpretation.

hixxy · Apr 1, 2012

Did you give the tool a go? I haven't been able to test it on any other machine other than this one as I can't tolerate any others (EMFs). Hopefully no dlls missing.

Yes I saw that, but I guess without any way to confirm them there's not much we can do? Besides maybe disregard VDR polymorphisms all together.

nanonug · Apr 1, 2012

hixxy82 said:
Did you give the tool a go? I haven't been able to test it on any other machine other than this one as I can't tolerate any others (EMFs). Hopefully no dlls missing.

I did, yes. It worked fine on Windows 7.

hixxy82 said:
Yes I saw that, but I guess without any way to confirm them there's not much we can do? Besides maybe disregard VDR polymorphisms all together.

Yeap, that is what I am pretty much doing, disregarding.

greenshots · Apr 5, 2012

The AHCY may not turn on homocysteine to drain through the CBS but everything else still drains thru there. The AHCY hides a CBS but doesn't negate it. You'll just see different homocysteine levels on lab tests so can't predict there's a CBS, like so many researchers are able to do based on the methylation test that includes so many types of folate, glutathione, etc.

That's one reason I don't put all my eggs in one basket and have just one test to guide me. If you just had that methylation testing done, you'd potentially dump in stuff like active folate, active P5P, methyl B12, etc., only to dump out thru a CBS hole and create even more excitotoxicity. For the record, thats what I think happens to those people who do so poorly on these supplements only to try liposomal glutathione later.

I'll PM you on the sulfur issue because my doc told me something about that issue.

Angela

hixxy82 said:
Thanks greenshots. You're a machine! I have suffered from a very severe intolerance of B6 that worsens my brain overstimulating. A lot of my neurological problems started over night with b6 for pyroluria. The funny thing is that I have 3 AHCY mutations one of them homozygous. Shouldn't this almost negate the affect of the CBS? Maybe I should look somewhere else for my B6 problem..... Maybe I have a GAD enzyme problem, but why on earth would it suddenly trigger off like that with B6 supplementation.

I suspected when I ordered the 23andme test that my results wouldn't be very nice, but I truely wish I hadn't got 2 homozygous COMTs! I suspected I would get at least one of these before the results came back. Can't I trade someone???

With the presence of the AHCY mutations, do I still need to treat my CBS? Does anyone here actually test their urine sulfite/sulfate? Maybe I can just bypass this and go onto treating the MT prefixed mutations. Just try muscle my way through it

Do you know what I think?? I think all this genetics talk and information needs a wiki. Heartfixer is good for a reference of some stuff, but is static and unchanging since 2008. That's a looong time ago for this kind of thing. Surely there should be some progress being made.

hixxy

Calico13 · Apr 11, 2012

I made this spreadsheet in google docs that might be helpful to those with 23andme data. https://docs.google.com/spreadsheet/ccc?key=0As5xqg3KuimidDZVRWxKa1gwS0p2a2ZhcnlGSGhPUnc

I took the Rs ID's from the other genetable provided in this thread and then translated the letters into what 23andme reports. This way you don't have to do the T=A, C=G thing. If you want added to this chart, you can just let me know in this thread instead of emailing me of course.

Now I have to admit I'm still pretty skeptical of some of these mutations that are deemed "bad". For a few of them, it is more common to have +/+ or +/- than to have -/-... Because of this, I put the frequency of each genotype at the very top, so you can see where you fall with the "normal" population. These frequencies were pulled directly from http://opensnp.org/.

Let me know if you see any errors also or if you have suggestions.

adreno · Apr 12, 2012

Calico13 said:
I made this spreadsheet in google docs that might be helpful to those with 23andme data. https://docs.google.com/spreadsheet/ccc?key=0As5xqg3KuimidDZVRWxKa1gwS0p2a2ZhcnlGSGhPUnc

I took the Rs ID's from the other genetable provided in this thread and then translated the letters into what 23andme reports. This way you don't have to do the T=A, C=G thing. If you want added to this chart, you can just let me know in this thread instead of emailing me of course.

Now I have to admit I'm still pretty skeptical of some of these mutations that are deemed "bad". For a few of them, it is more common to have +/+ or +/- than to have -/-... Because of this, I put the frequency of each genotype at the very top, so you can see where you fall with the "normal" population. These frequencies were pulled directly from http://opensnp.org/.

Let me know if you see any errors also or if you have suggestions.

Thank you for this, Calico. It does indeed look like a lot of those polymorphisms are quite common. For instance, almost 50% has the CBS and BHMT upregulation, that we are told is so bad.

nanonug · Apr 12, 2012

adreno said:
It does indeed look like a lot of those polymorphisms are quite common. For instance, almost 50% has the CBS and BHMT upregulation, that we are told is so bad.

Personally, as of right now, I am mostly focusing on the MTHFR polymorphisms. These are the ones with the most research attached to them and they come with very concrete health consequences. One of the problems I have with many of the other Yasko polymorphisms is that research is either very thin or non-existent.

adreno · Apr 12, 2012

nanonug said:
Personally, as of right now, I am mostly focusing on the MTHFR polymorphisms. These are the ones with the most research attached to them and they come with very concrete health consequences. One of the problems I have with many of the other Yasko polymorphisms is that research is either very thin or non-existent.

But even MTHFR mutations are extremely common. 64% have mutations in the C677T snp. Could there really be a defect in 2/3 of the gene pool? I read somewhere that that these mutations are there to protect from cancer, due to hypermethylation.

nanonug · Apr 12, 2012

adreno said:
But even MTHFR mutations are extremely common. 64% have mutations in the C677T snp. Could there really be a defect in 2/3 of the gene pool? I read somewhere that that these mutations are there to protect from cancer, due to hypermethylation.

Well, a few things come to mind:

Human animals were not supposed to live much beyond reproductive age. Mutations that might have a net benefit in the first 30 years of life (not getting certain cancers during this time period, for instance) might not be so useful when those same animals want to live to be 100.
Being heterozygous for just the one C677T mutation doesn't appear to be that bad overall. The same, however, doesn't appear to be true for its cousin A1298C. Strict heterozygosity of the latter is associated with spontaneous abortions, in much higher rates than any other MTHFR screw up. Note that 677TT, however, has a much lower frequency, owing to its detrimental effects.
From what I've read, cancer appears to be associated with local hypermethylation and global hypomethylation. Now, if MTHFR screw ups also lead to local hypomethylation, that right there might explain their "net benefit" in terms of cancer. However, absolute global hypomethylation (without local exceptions) will just lead to expression of "junk" DNA, including that of "dormant" retroviruses. This is hardly a recipe for healthy longevity.
The increased levels of environmental pollution probably put a great deal of strain on the methylation cycle, with the need to divert more and more homocysteine into the transsulfuration (glutathione) pathway. When these polymorphisms propagated in the gene pool, this problem did not exist, I would posit.
Finally, folic acid and folic acid fortification programs did not exist when these polymorphisms propagated in the gene pool. Given that unmetabolized folic acid is known to wreak havoc in people with MTHFR mutations, this could be the single most important reason for the "modern" problems.

adreno · Apr 12, 2012

Nanonug, would you take a look at my SNPs, and tell me what you think?

http://forums.phoenixrising.me/showthread.php?t=17198

nanonug · Apr 12, 2012

adreno said:
Nanonug, would you take a look at my SNPs, and tell me what you think?
http://forums.phoenixrising.me/showthread.php?t=17198

I must confess that I avoided that thread so far, mostly because of my recently developed belief that those polymorphisms, with the possible exception of MTHFR and maybe a couple more, don't tell the whole story.

Focusing on just those two CBS polymorphisms, one might get the false impression, following Yasko, that everything goes down the transsulfuration pathway. But what about the dozen or so other CBS polymorphisms that reduce the enzyme catabolic activity? What happens when one has both up- and down-regulation polymorphisms? And why is Yasko not looking at downregulation? After all, glutathione depends on this pathway and a downregulation could lead to a lot of oxidative stress with all that this entails.

I must say that I am now an official skeptic of Yasko's methodology as it is currently designed. This is a change of mind from a month or so ago. But until I see the proper research done or published, I cannot just trust one persons word.

Calico13 · Apr 12, 2012

adreno said:
Thank you for this, Calico. It does indeed look like a lot of those polymorphisms are quite common. For instance, almost 50% has the CBS and BHMT upregulation, that we are told is so bad.

...

But even MTHFR mutations are extremely common. 64% have mutations in the C677T snp. Could there really be a defect in 2/3 of the gene pool? I read somewhere that that these mutations are there to protect from cancer, due to hypermethylation.

Nanonug said:
I must say that I am now an official skeptic of Yasko's methodology as it is currently designed. This is a change of mind from a month or so ago. But until I see the proper research done or published, I cannot just trust one persons word.

I'm just so glad to see others questioning these things. It's a sigh of relief to be honest.

My results are patient 1 on the spreadsheet and none of mine are really all that rare or concerning to me. I guess the double ++ COMT is somewhat interesting and probably explains why I'm jumpy, "type A" and have higher norepinephrine levels, but I really don't know. I do tend to need high doses of B12, so that correspond somehow.

If anyone wants to do extended shares on 23andme, to compare our health and drug traits, just let me know. I'll PM you a link to my profile on there.

I actually wonder more about other SNP's, like our liver pathways and such. I may end up making a new thread about this if either of you are interested. Are you two slow or fast caffeine metabolizers? The SNP is rs762551

I am CC, which is the "bad" +/+ one if we want to use Yasko speak. lol The frequency of having CC is ~8-14% depending upon where you look. This seems more significant than some of the 50% frequency Yasko ones. ;-) Edit: CYP1A2 metabolizes more than just caffeine too.

Extract SNPs from 23andme data to yasko/nutrigenomics notation

greenshots

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froufox

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hixxy

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nanonug

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hixxy

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hixxy

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hixxy

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nanonug

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nanonug

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hixxy

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nanonug

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greenshots

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Calico13

adreno

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nanonug

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adreno

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nanonug

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adreno

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nanonug

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Calico13