Extract SNPs from 23andme data to yasko/nutrigenomics notation

[snowathlete]

So, now it's time to go to the heartfixer website to see what all this means!

Absolutely - onto what this all means! I dont want to hijack this thread, so, here is a seperate thread i just started about my three dodgy genes.

 

[hixxy]

Okay, I redid mine using the spreadsheet as a guide for what is + or -.


ACE DEL16 No Data
CBS A360A -/- (GG)
CBS C699T +/- (AG)
COMT H62H +/+ (TT)
COMT V158M +/+ (AA)
COMT L136L No Data
COMT P199P -/- (GG)
MAO-A R297R + (T)
MTHFR C677T +/+ (TT)
MTHFR A1298C -/- (TT)
MTHFR P39P -/- (GG)
MTR A2756G -/+ (AG)
MTRR H595Y -/- (CC)
MTRR K350A -/- (AA)
MTRR R415T -/- (CC)
MTRR S257T No Data
MTRR A66G +/+ (GG)
MTRR-11 A664A +/- (AG)
NOS-3 G894T No Data
SUOX S370S No Data
SUOX A628G No Data
VDR TAQ -/- (CC)
VDR FOK No Data
ACAT1-02 -/- (GG)
AHCY-01 +/+ (CC)
AHCY-02 -/+ (AG)
AHCY-19 +/- (CT)
BHMT-01 No Data
BHMT-02 -/- (CC)
BHMT-04 -/- (AA)
BHMT-08 -/- (CC)
SHMT C1420T -/- (GG)

Still seems very nasty, at least there's only one MTHFR now. Still got that nasty 2 COMT homozygous! Wondering if this is why I have absolutely no tolerance of 5MTHF and MB12.

 

[hixxy]

What is the best reference for interpreting 23andme raw data? How were the + or - genotypes determined that were put in that spreadsheet?

nanonug: As far as looking up P450 SNPs (or any others for that matter) it seems like a cumbersome process trying to figure out exactly which SNPs are important and which are not. when looking up CYP1A1, there is a very loooong list, a lot of which don't have very much information in SNPedia at all.

When looking up an SNP in the 23andme raw data browser, there is a dbSNP orientation field (plus or minus). Any idea what the significance of this is? It seems to correlate with the results I pasted, so I presume I could have just looked them all up there without interpreting them.

I looked up GSTM1 and found that pretty much all the SNPs listed there were positive. No idea of the significance.

Is SNPedia the best resource out there?

 

[snowathlete]

When looking up an SNP in the 23andme raw data browser, there is a dbSNP orientation field (plus or minus). Any idea what the significance of this is? It seems to correlate with the results I pasted, so I presume I could have just looked them all up there without interpreting them.

I may be wrong but I think the + and - meaning on 23andme is totally independent and not related to what + and - mean on the yasko stuff.

It's to do with whether a gene is recorded as AC or TG. In the DNA double helix when you look at the rungs of the ladder across it, it's a question of which side you are looking from (orientation) ; Look from one side and you call it A look from the other and it's T. Same for C and G. Rather than calling these sides left or right they call them + or -.
Someone needs to confirm if I am right, I could be wrong about this.

The + or - noted in the yasko spreadsheet means whether a result is good or bad, hence + or -.

 

[nanonug]

Okay, I redid mine using the spreadsheet as a guide for what is + or -.
Still seems very nasty, at least there's only one MTHFR now. Still got that nasty 2 COMT homozygous! Wondering if this is why I have absolutely no tolerance of 5MTHF and MB12.

I checked and everything appears to be in accordance with the spreadsheet. Now, off to the heartfixer website for interpretation!

 

[nanonug]

What is the best reference for interpreting 23andme raw data? How were the + or - genotypes determined that were put in that spreadsheet?

That spreadsheet was put together by "someone else". I don't know who it was but to the best of my abilities, it appears to be "accurate". I don't trust the spreadsheets interpretation of VDR though.

As sources for my own research, I tend to use snpedia, pubmed, dbsnp and omin.

As far as looking up P450 SNPs (or any others for that matter) it seems like a cumbersome process trying to figure out exactly which SNPs are important and which are not. when looking up CYP1A1, there is a very loooong list, a lot of which don't have very much information in SNPedia at all.

Yes, it is a lot of work. The thing is that we are kind of pioneers here. It's a brave new and mostly unexplored world, not unlike what North America and Australia used to be!

When looking up an SNP in the 23andme raw data browser, there is a dbSNP orientation field (plus or minus). Any idea what the significance of this is?

I don't know and I have been too lazy to look it up. I know that an "A" allele in minus orientation corresponds to a "T" allele in plus orientation. Similar thing for the "C" allele.

I looked up GSTM1 and found that pretty much all the SNPs listed there were positive. No idea of the significance.

By positive, do you mean with mutations?

Is SNPedia the best resource out there?

See above.

 

[hixxy]

Positive in that dbSNP orientation is plus. So if dbSNP DOES correlate to positive for that SNP, then I have serious problems in GSTM1. If I crossreference my above posted results with the dbSNP orientation field, it seems they DO correlate. The field will be plus if you are either homozygous or herterozygous positive for the SNP.

I do hope my interpretation is rock solid, as I'm going to take these results to the doctor with me on Friday. It certainly sheds some light on why I have such a horrendous time supplementing almost anything in relation to the methylation cycle. I'm one of these people whose body rejects almost anything you throw at it.

The annoying thing is, recommendations for the 2 COMT homozygous positive SNPs I have is to supplement hydroxocobalamin -- but -- I suspect my glutathione is likely way too low for the enzyme that activates hydroxocobalamin to methylcobalamin to work, therefore this is kind of useless, but supplementing methylcobalamin will overload me with methyl groups.

Such a painful network in interrelated nightmares.

 

[hixxy]

So full of questions -- in COMT H62H COMT is the gene, what do you call H62H? The SNP?

 

[nanonug]

Positive in that dbSNP orientation is plus. So if dbSNP DOES correlate to positive for that SNP, then I have serious problems in GSTM1

No, that's not it! I think, but I could be wrong, that the orientation has to do with the way they look at the chromosomes.

The annoying thing is, recommendations for the 2 COMT homozygous positive SNPs I have is to supplement hydroxocobalamin -- but -- I suspect my glutathione is likely way too low for the enzyme that activates hydroxocobalamin to methylcobalamin to work, therefore this is kind of useless, but supplementing methylcobalamin will overload me with methyl groups.

Yes, you are correct. However, there is hope. You can supplement with acetyl-glutathione (something I use myself) or liposomal glutathione (something I have never used but some other people here use).

 

[nanonug]

So full of questions -- in COMT H62H COMT is the gene, what do you call H62H? The SNP?

H62H is the variation for a specific gene. Look at what SNPedia has to say: rs4633.

 

[hixxy]

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]

Hi everyone,

I just wondered if anyone might know the answer to my question....I was tested at RedLabs for MTHFR 1298A/C and 677C/T, and the results were homozygous for 1298 (which they have classed as "high activity") and 677C was heterozygote (and classed as "moderate activity"). They seem to give different results to Amy Yasko, who I have not been tested with yet.

Re the 1298, does high activity mean that I have the normal version?

Thanks a lot.

 

[hixxy]

I suspect how the activity is how well the enzyme is functioning?

This question was also asked here: http://forums.phoenixrising.me/showthread.php?10006-MTHFR-Polymorphism-test

They didn't seem to resolve the issue though as far as I can see on a quick read. Have you tried asking Red Labs to clarify?

Seems heterozygous is always positive for the mutation, but homozygous can be both homozygous positive or homozygous negative.

This would make sense with how your activity is reported. The high activity might correlate to homozygous negative, while heterozygous positive would result in reduced activity.

If you've read the rest of the thread, you will understand I'm by no means an expert tho !!!

Also, going by rich's post on that thread, testing MTHFR alone may not be as helpful as testing it alongside the other methylation genes. Seems it's combinations of genes that would play a role in ME, not single genes.

 

[hixxy]

Although, http://www.lrjournal.com/article/S0145-2126%2808%2900561-4/abstract mentions that low activity MTHFR geneotypes resultedi n low relapse of acute lymphoblastic leukemia.

So maybe I have it backwards? Sigh. Or completely wrong!

 

[nanonug]

I was tested at RedLabs for MTHFR 1298A/C and 677C/T, and the results were homozygous for 1298 (which they have classed as "high activity") and 677C was heterozygote (and classed as "moderate activity"). Re the 1298, does high activity mean that I have the normal version?

This is why I dislike these types of tests. Instead of providing alleles and interpretation, they just provide interpretation, leaving one to guess as to the alleles.

My "guess" is that "high activity" means you have the "normal" alleles, i.e, no mutation. I base this "guess" on the fact that mutations result in lower activity enzymes.

 

[nanonug]

Although, http://www.lrjournal.com/article/S0145-2126%2808%2900561-4/abstract mentions that low activity MTHFR geneotypes resultedi n low relapse of acute lymphoblastic leukemia.

I tried to understand the damn abstract but I am not sure that I could. OK, let me clarify, I didn't. It's too convoluted.

 

[hixxy]

I wonder if using B3 to mop up excess methyl groups would be effective in then allowing you to supplement methylb12 if you have COMT mutations.

 

[froufox]

Thanks everyone! :Retro smile: & thanks hixxy I remember seeing that thread. That is what i thought too...that the high activity meant that the enzyme was functioning normally...and that homozygous can be either positive or negative.

Yeah agree Nanonug, its a bit frustrating - I did contact RedLabs twice to ask them about the "high" and "moderate" classification, but all they said was that the high activity meant homozygous and my moderate result equalled heterozygous, so I'm assuming that it is homozygous negative, but I'll have to write to them again to be sure.

I just had that one done as I couldnt afford Amy Yasko's panel methylation panel at the time...I do want to get her panel done at some point....I know that her lab is getting different results to RedLabs eg the VDR one....so it will be interesting to see if any of the MTHFR ones differ to RedLabs.

 

[greenshots]

Yes, I think that is why you have no tolerance for those supplements. the Combo of the COMT +/+ along with the VDR Taq -/- means you're a super COMT (as I refer to them). If you have the COMT L136L +/+ defect, it might help you just a tiny smidge but this combo usually means trouble with methyl donors. You might be able to take them but I would think it would be very teensy doses.

Your COMT C677T +/+ is a bummer because you need 5 MTHF so badly yet can't tolerate the methyl donors too much. I would try them in the most tiny doses you have ever seen to get that bad boy working again!

You need B-12 badly but I doubt MB12 would be tolerated and if you have to pick your battles here, I'd pick the active folate in teensy doses and hydroxy B12, which you'll still probably react to but its better than the methyl reaction you'd have.
Thats my two cents.
Angela

Okay, I redid mine using the spreadsheet as a guide for what is + or -.


ACE DEL16 No Data
CBS A360A -/- (GG)
CBS C699T +/- (AG)
COMT H62H +/+ (TT)
COMT V158M +/+ (AA)
COMT L136L No Data
COMT P199P -/- (GG)
MAO-A R297R + (T)
MTHFR C677T +/+ (TT)
MTHFR A1298C -/- (TT)
MTHFR P39P -/- (GG)
MTR A2756G -/+ (AG)
MTRR H595Y -/- (CC)
MTRR K350A -/- (AA)
MTRR R415T -/- (CC)
MTRR S257T No Data
MTRR A66G +/+ (GG)
MTRR-11 A664A +/- (AG)
NOS-3 G894T No Data
SUOX S370S No Data
SUOX A628G No Data
VDR TAQ -/- (CC)
VDR FOK No Data
ACAT1-02 -/- (GG)
AHCY-01 +/+ (CC)
AHCY-02 -/+ (AG)
AHCY-19 +/- (CT)
BHMT-01 No Data
BHMT-02 -/- (CC)
BHMT-04 -/- (AA)
BHMT-08 -/- (CC)
SHMT C1420T -/- (GG)

Still seems very nasty, at least there's only one MTHFR now. Still got that nasty 2 COMT homozygous! Wondering if this is why I have absolutely no tolerance of 5MTHF and MB12.

 

[greenshots]

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

This is why I dislike these types of tests. Instead of providing alleles and interpretation, they just provide interpretation, leaving one to guess as to the alleles.

My "guess" is that "high activity" means you have the "normal" alleles, i.e, no mutation. I base this "guess" on the fact that mutations result in lower activity enzymes.