Anybody with ME/CFS also positive for glucose-6-phosphate dehydrogenase deficiency?

[mgk]

@mgk my list is very different to yours. Which version of the 23andme chip were you tested on? Mine was the version 3 chip

I think it's version 4 because I had it done January of this year. I'm not sure though. I can't seem to find where it says on the site.

 

[flutter]

mgk with regard to 23andme having 4 of the pathogenic snps, have you looked at all the i numbers as well as the rs numbers? My 23andme result for the G6PD gene has 59 snps, 37 of them are i numbers which need more digging to find their corresponding rs numbers

Hi Sea, Trying to determine if I have the G6PD Deficiency based on my results here. These are the SNP's I'm homozygous for :
G6PD rs35972742 G GG +/+
G6PD rs5030870 C CC +/+
G6PD rs72554664 C CC +/+
If I have the C Allele for the rs72554664 SNP does that mean it is not the "bad" version because it's not "T" allele?
Is there a place I can run my 23&me results to see if I have this mutation? I ran this through Livewello but found that the list contains Benign SNP's so it's extremely hard to decipher. I only want to know if I have the "bad" SNP's related to G6PD Deficiency. Thanks

 

[Sea]

Hi Sea, Trying to determine if I have the G6PD Deficiency based on my results here. These are the SNP's I'm homozygous for :
G6PD rs35972742 G GG +/+
G6PD rs5030870 C CC +/+
G6PD rs72554664 C CC +/+
If I have the C Allele for the rs72554664 SNP does that mean it is not the "bad" version because it's not "T" allele?
Is there a place I can run my 23&me results to see if I have this mutation? I ran this through Livewello but found that the list contains Benign SNP's so it's extremely hard to decipher. I only want to know if I have the "bad" SNP's related to G6PD Deficiency. Thanks

If you've been tested in the last year or so it would have been on version 4 of 23andme's chip so you can look at mgk's list earlier in this thread for the pathogenic alleles.

If you were tested before that, on version 3, the list of tested snps is quite different for this gene and you would have to do the digging yourself. It's not one I've done yet.

To find information you need to look at dbSNP
http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
From your 23andme browse raw data page type G6PD into the gene search bar
Any snps that have an rs number are linked directly to dbsnp by clicking on the dropdown menu at the left of the row.
Any snps that have an i number you have to find information by looking at the chromosome position instead. Mgk has explained how to do this earlier in this thread

OMIM is a great resource for finding which snps are well studied in an illness too.

http://omim.org/search?index=entry&sort=score+desc,+prefix_sort+desc&start=1&limit=10&search=G6pd

 

[Plum]

would Prometheus or livewello pick this up?

I've just done a Variance report through Livewello for this and it comes up with quite a few. Type G6PD into the sandbox box to get the list of snps and run the report.

 

[Clairemont]

Hi Sea, Trying to determine if I have the G6PD Deficiency based on my results here. These are the SNP's I'm homozygous for :
G6PD rs35972742 G GG +/+
G6PD rs5030870 C CC +/+
G6PD rs72554664 C CC +/+
If I have the C Allele for the rs72554664 SNP does that mean it is not the "bad" version because it's not "T" allele?
Is there a place I can run my 23&me results to see if I have this mutation? I ran this through Livewello but found that the list contains Benign SNP's so it's extremely hard to decipher. I only want to know if I have the "bad" SNP's related to G6PD Deficiency. Thanks

Wondering if you ever got an answer to this... I've searched in vain. I have the same polymorphisms (and no other) and I find that suspect and wonder if 23andMe could have made an error. Of course, life is weird.

 

[Lynn_M]

According to http://omim.org/entry/305900#0029, the A (= T) is the risky version of rs72554664. So having a C allele for this snp means you don't have the bad version. They list a number of other snps associated with G6PD deficiency, but they don't list your first two, rs35972742 and rs5030870.

If you drop down to the bottom of the screen for
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=72554664, they show that close to zero no A alleles were found in the population base that was studied.

 

[Clairemont]

According to http://omim.org/entry/305900#0029, the A (= T) is the risky version of rs72554664. So having a C allele for this snp means you don't have the bad version. They list a number of other snps associated with G6PD deficiency, but they don't list your first two, rs35972742 and rs5030870.

If you drop down to the bottom of the screen for
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=72554664, they show that no A alleles were found in the population base that was studied.

Thank you; I missed that " G-to-A mutation" reference in the first one (brain fog?), and I don't understand what you mean by the second comment. I have looked at that reference and can not make heads or tails of it. Obviously I need to go to school on making sense of this stuff. Do you have any videos or other "genes for dummies" that you recommend?

From what I can tell, versions I do have are likely fairly rare. If that's the case, I wonder what the likelihood is that they might cause a problem, and if I've had symptoms (which could be the result of something else), does it make sense to get tested? I wonder about that generally with rarely found mutations.

 

[Lynn_M]

Clairemont,
Regarding my second reference, scroll down as far as you can on that screen. You'll seen a heading with a purple background that says: "Population Diversity (Alleles in RefSNP orientation). See additional population frequency from 1000Genome...". Underneath that is another heading of: Sample Ascertainment Genotypes Allele, and underneath that is another subheading.

In the subheading, Population means the ethnicity of the population studied. So EUR is European, AFR is African, and I'm not sure of the others. Then you have Chrom. Sample Count. That is how large each sample was. In this case, under Alleles, if anyone in each particular sample had an A allele, part of the bar graph would be green. If anyone had a G allele, that part of the bar graph would be gray. Above each bar graph are numbers representing the portion of population that had an A allele and the portion that had a G allele. I misspoke above when I said no A alleles were found, because I was just looking at the color of the graph and didn't look at the numbers. The number of A alleles found in the EAS was too small to show up on the bar.

Actually, for the EAS population studied for rs72554664, .0050 had an A allele, and .9950 had a G allele. So 99.5% of that population had a G allele. For the aggregated populations, .0004 had an A allele and .9996 had a G allele.

I also looked up the population diversity for the other 2 snps you listed on dbSNP, which is the shorthand name for that second reference site. For rs5030870, with an aggregated population sample of 121,410 chromosomes, there were no A alleles found. For rs35972742, the sample size is 2 chromosomes, identified as Watson, which I presume is the famous Dr. Watson of double helix fame. He was GG.

Based on the limited information that shows on dbSNP, it seems these snps have not been studied much. I don't know why you think your versions are likely fairly rare. From what I see on dbSNP, I would conclude that you have the most common versions of these 3 snps. If you have symptoms that you think might be due to G6PD, it might be from the other G6PD snps that are discussed on the OMIM link I gave. My v.3 23andMe results lists 59 different G6PD snps.

When you look at your raw data on 23andMe, if you look at the far left side of the line for each snp, you'll see a little plus sign in a box. If you click on the + sign one time, a drop-down menu appears, and one of the choices in that menu is dbSNP lookup. Clicking on dbSNP is an easy way to check out how common your alleles are. SNPedia also has a more simplified chart of how often allele combinations appear in various population groups. I also like to click on Google Scholar (SNP) and Google Scholar(Gene) to get more information.

To look at the population diversity for a well studied gene, MTHFR C677T, look at
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=1801133.

I don't know of any guide for how to use these gene interpretation tools. I agree there is a need for one. I think someone posted a tutorial about genes on the blogs.

 

[Lynn_M]

Claremont,

JamieS has posted a 6-part series on the Community Blog about snps and 23andMe and ME/CFS. Go here for the start of the series.

 

[Clairemont]

Clairemont,
Regarding my second reference, scroll down as far as you can on that screen. You'll seen a heading with a purple background that says: "Population Diversity (Alleles in RefSNP orientation). See additional population frequency from 1000Genome...". Underneath that is another heading of: Sample Ascertainment Genotypes Allele, and underneath that is another subheading.

In the subheading, Population means the ethnicity of the population studied. So EUR is European, AFR is African, and I'm not sure of the others. Then you have Chrom. Sample Count. That is how large each sample was. In this case, under Alleles, if anyone in each particular sample had an A allele, part of the bar graph would be green. If anyone had a G allele, that part of the bar graph would be gray. Above each bar graph are numbers representing the portion of population that had an A allele and the portion that had a G allele. I misspoke above when I said no A alleles were found, because I was just looking at the color of the graph and didn't look at the numbers. The number of A alleles found in the EAS was too small to show up on the bar.

Actually, for the EAS population studied for rs72554664, .0050 had an A allele, and .9950 had a G allele. So 99.5% of that population had a G allele. For the aggregated populations, .0004 had an A allele and .9996 had a G allele.

I also looked up the population diversity for the other 2 snps you listed on dbSNP, which is the shorthand name for that second reference site. For rs5030870, with an aggregated population sample of 121,410 chromosomes, there were no A alleles found. For rs35972742, the sample size is 2 chromosomes, identified as Watson, which I presume is the famous Dr. Watson of double helix fame. He was GG.

Based on the limited information that shows on dbSNP, it seems these snps have not been studied much. I don't know why you think your versions are likely fairly rare. From what I see on dbSNP, I would conclude that you have the most common versions of these 3 snps. If you have symptoms that you think might be due to G6PD, it might be from the other G6PD snps that are discussed on the OMIM link I gave. My v.3 23andMe results lists 59 different G6PD snps.

When you look at your raw data on 23andMe, if you look at the far left side of the line for each snp, you'll see a little plus sign in a box. If you click on the + sign one time, a drop-down menu appears, and one of the choices in that menu is dbSNP lookup. Clicking on dbSNP is an easy way to check out how common your alleles are. SNPedia also has a more simplified chart of how often allele combinations appear in various population groups. I also like to click on Google Scholar (SNP) and Google Scholar(Gene) to get more information.

To look at the population diversity for a well studied gene, MTHFR C677T, look at
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=1801133.

I don't know of any guide for how to use these gene interpretation tools. I agree there is a need for one. I think someone posted a tutorial about genes on the blogs.

Thanks for the breakdown. I'll have to study that. I did look at the SNP distribution on Livewello and that's how I came up with the relatively rare comment. (I always look at the distribution they provide; it's one of the first things that I do.) So I don't know what's going on with that.

 

[Lynn_M]

Clairemont,
Whoever created that template on Livewello got it backwards. If you look at the comments at Livewello for G6PD, FO4547 commented there 5 months ago that the template had the minor alleles reversed. dbSNP is an authoritative source. Any template at Livewello - needs to be doublechecked.

Did you run your snps through Promethease? They will highlight variant snps for G6PD.

 

[Clairemont]

Clairemont,
Whoever created that template on Livewello got it backwards. If you look at the comments at Livewello for G6PD, FO4547 commented there 5 months ago that the template had the minor alleles reversed. dbSNP is an authoritative source. Any template at Livewello - needs to be doublechecked.

Did you run your snps through Promethease? They will highlight variant snps for G6PD.

I'm confused. Are my alleles reversed or are the percentages reversed?

G6PD rs35972742 GG
G6PD rs5030870 CC
G6PD rs72554664 CC

Does that mean I don't have a mutated rs72554664? (EDIT: see next comment.)

The reason I ask is that I wrote to the Genetic and Rare Diseases (GARD) Information Center asking whether rs35972742, rs5030870, and rs72554664 gene mutations cause G6PD deficiency?
And they responded: "According to ClinVdeficiency (i.e., be pathogenic). ar the rs72554664 gene mutation may contribute to G6PD," and that I should talk over whether to be tested with my doctor.

Thanks.

 

[Clairemont]

Just remembered to look at Promethease. And rs72554664CC shows up as GG, a common clinvar.

Sheesh.

And thanks. That saves me £. (And I definitely need to learn to read dbSNP.)

 

[Lynn_M]

Clairemont,
It's still possible that you might have some other G6PD snp that is a minor allele and would be pathogenic.

When you say rs72554664 GG is a common clinvar, I'm not sure what a clinvar is. Based on the percentages dbSNP gives, I would say CC is the wild snp for that rs#.

Did the GARD say which allele for rs72554664 was pathogenic? That would have been a lot more helpful than saying a mutation in rs72554664 can contribute to G6PD, but not telling you which was the mutation.

 

[Clairemont]

Clairemont,
It's still possible that you might have some other G6PD snp that is a minor allele and would be pathogenic.

When you say rs72554664 GG is a common clinvar, I'm not sure what a clinvar is. Based on the percentages dbSNP gives, I would say CC is the wild snp for that rs#.

Did the GARD say which allele for rs72554664 was pathogenic? That would have been a lot more helpful than saying a mutation in rs72554664 can contribute to G6PD, but not telling you which was the mutation.

No, they didn't say, but I told them what I supposedly had. Clinvar... hmmm, it's either a word Promethease uses when referring to a group. (So I assumed it means common variable.)

 

[Lynn_M]

Clairemont,

When you said rs72554664 GG was a common clinvar, what came to my mind was that rs72554664 is listed on the ClinVar web site as a pathogenic allele - see http://www.ncbi.nlm.nih.gov/clinvar/variation/100059/. However, it is the AA allele that is the gene mutation and pathogenic. If you look at the dbSNP website, you can also see that in the Clinical Significance box at the top, it says, With Pathogenic allele [ClinVar].

 

[Sea]

I'm confused. Are my alleles reversed or are the percentages reversed?

G6PD rs35972742 GG
G6PD rs5030870 CC
G6PD rs72554664 CC

Does that mean I don't have a mutated rs72554664? (EDIT: see next comment.)

The reason I ask is that I wrote to the Genetic and Rare Diseases (GARD) Information Center asking whether rs35972742, rs5030870, and rs72554664 gene mutations cause G6PD deficiency?
And they responded: "According to ClinVdeficiency (i.e., be pathogenic). ar the rs72554664 gene mutation may contribute to G6PD," and that I should talk over whether to be tested with my doctor.

Thanks.

You don't have a mutated rs72554664 if 23andme says it is CC.
You will notice on the dbsnp page
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs72554664
that the reference alleles are A/G (REV)
That means this snp is read on the minus or reverse strand. 23andme snps are all reported on the positive strand. When translating your 23andme results for a reverse strand snp A is T and vice versa, C is G and vice versa.

So if your 23andme result is CC for this snp (positive strand) then it is GG (negative strand) according to dbsnp and is the common result.

Clinical variant just means one of the alternatives for this snp. Both the common allele and the mutation are clinical variants.

 

[Clairemont]

You don't have a mutated rs72554664 if 23andme says it is CC.
You will notice on the dbsnp page
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs72554664
that the reference alleles are A/G (REV)
That means this snp is read on the minus or reverse strand. 23andme snps are all reported on the positive strand. When translating your 23andme results for a reverse strand snp A is T and vice versa, C is G and vice versa.

So if your 23andme result is CC for this snp (positive strand) then it is GG (negative strand) according to dbsnp and is the common result.

Clinical variant just means one of the alternatives for this snp. Both the common allele and the mutation are clinical variants.

Thanks.

I knew that the alleles might be translated differently, but I didn't know how (or why and so it seems illogical... why would Livewello report it for other than how we should be able to look it up?).

So that being the case, based on my reading of Livewello's pie chart, my cc or gg, though a small percentage is a homozygous mutation (it's in red), it's not pathogenic. (Or should I be switching the red to green for some reason?)

However, a male with a G/A result likely would be and a female with an AA result likely would be (based on what is required for a pathogentic expression of G6pd).

Is that right?

 

[Valentijn]

So that being the case, based on my reading of Livewello's pie chart, my cc or gg, though a small percentage is a homozygous mutation (it's in red), it's not pathogenic.

If Livewello shows CC or GG as being rare, they are completely wrong. CC/GG is the version which 99.5%-100% of people have.

You can see that data on dbSNP at http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs72554664 . If Livewello contradicts dbSNP, then Livewello is going to be the one which is wrong. And in this case it certainly does look like the data at https://livewello.com/snp/rs72554664 is completely incorrect.

 

[Sea]

Thanks.

I knew that the alleles might be translated differently, but I didn't know how (or why and so it seems illogical... why would Livewello report it for other than how we should be able to look it up?).

So that being the case, based on my reading of Livewello's pie chart, my cc or gg, though a small percentage is a homozygous mutation (it's in red), it's not pathogenic. (Or should I be switching the red to green for some reason?)

Your CC/GG should be green. You don't have a mutation. Livewello is wrong here.

However, a male with a G/A result likely would be and a female with an AA result likely would be (based on what is required for a pathogentic expression of G6pd).

Is that right?

Sorry I don't understand what you're asking here