Genetic profile results

[rollercoaster]

I have my raw data from 23andMe and also my geneticGenie profile.

My hypothesis is that my POIS is caused by a hyperactive immune system which is in-turn caused by genetic mutations.

Why do I think so?

• I had a cysts removed from my cheek bone twice in a period of 5 years when I was between ages 13-19
• I have had massive outbursts of hives all over my body due to acidity during childhood
• I suffered from severe pulmonary tuberculosis when I was 25 (over 3 liters of fluid removed from lungs in 3 times, doctors were surprised too. treatment lasted for 9 months). I suspect it was because of hyper-active immune response. Source - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052244/
• I have suffered from POIS since puberty
• Taking antihistamine  after O has reduced my symptoms by 70% for me in the past. Only tried it a couple of times till now
• I have always had allergic rhinitis since teenage and sinus related problems in the past

All this leads me to believe that the root cause of my POIS is related to an overactive immune response.
How can I get to know if I have any genetic variation that causes this hyperactive immunity? I cannot interpret the results of genetic genie profile.
Is there any company / website out there that can help me figure this out from my raw data?
Thanks

Methylation report from Genetic Genie attached.

[Clues]

Rollercoaster, in my case it also very much seems like my immune system (and nervous system?) is overly sensitive. However based on my limited understanding, the cause isn't necessarily genetic. I've read in various places that it's possible for the immune system to become overly sensitised to various triggers. For example, see the very recent post somebody made about the cause of IBS.

Maybe it's possible for the immune system to be desensitised somehow. This is my biggest hope at the moment. I'm trying out the Wim Hof method with this in mind, but the results are inconclusive so far. I'm less sensitive to cold, and to light exercise, but orgasm triggers the same symptoms as before.

[Iwillbeatthis]

Why getting your whole genome sequenced can be unhelpful by Dr Amy Yasko - one of the pioneers of the methyl cycle:

"There is one final critical point that needs to be reiterated with respect to SNP testing. There are approximately 25,000 genes in the human genome. Dr.Yasko personally believes in only looking at SNPs that are in well defined pathways where it is clear how to add nutritional support to bypass imbalances. Having a laundry list of SNPs without a way to use nutritional support is not consistent with the way she approaches health. So, whether you have a test that gives you 1000 or 5000 SNPs this is still only a fraction of the total number of genes in your body and frankly having more SNPs is not the issue. The real question is whether the SNPs you have are in a pathway that has been characterized so you know what to do to help restore your body to health. The reason Dr.Yasko focuses on the methylation cycle is that it is a well defined pathway, it is very clear where nutritional support can bypass mutations and the pathway we look at IS the system the body uses to edit and correct problems with other genes. So regardless of how many other SNPs there are in the 25,000 or so other genes in the body, IF those genes are regulated by methylation, then having your methylation cycle in balance gives you the tools you need to help to turn on or off those other genes that are NOT part of the 30 SNP methylation panel. This is called epigenetics, and Dr.Yasko has given entire talks just on this topic. Having the methylation cycle function optimally and bypassing SNPs in this pathway allows the global editing function in your body to help to correct issues with any number of other genes in the system. THIS is why this pathway is so critical for health and wellness."

"Recall that every cell in your body contains identical DNA, which is why blood, saliva, hair, fingernails can be used to evaluate your personal DNA. There are approximately 25,000 genes in the human body that code for proteins, but it is not practical to look at all 25,000 genes. While every cell in the body contains the information about your total genetic profile, tests that look at genetics choose specific genes to evaluate and look for changes or mutations. I personally believe in only looking for changes in the DNA in well-defined nutritional pathways where it is clear how to add natural supplements to bypass imbalances. I feel that whether you have a test that gives you 30 or 1000 or 5000 markers this is still only a fraction of the total number of genes in your body and frankly having more markers is not the issue. The real question is whether the information that you have is in a pathway that has been characterized so you know what to do to help restore your body to health. The nutritional pathway that this program focuses on is something I call “The Methylation Cycle”. The methylation cycle is a well-defined nutritional pathway in the body. When you look at the suggested nutritional support, you are working to increase the ability of the entire Methylation Cycle to run properly, keeping in mind that it has been functioning to some degree in spite of any mutations in particular genes. Nutrigenomics is just one aspect of the factors that determine your health. I see complex health conditions as multifactorial in nature. That means that while your nutrigenomics are a piece of the puzzle they are not the whole picture. The environmental burden of toxins you are exposed to, along with infectious agents (viruses, bacteria, fungal infections, yeast) and the stress on your system all impact your overall health."

[Quantum]

Hi IWBT,
What I understand from this comment from Dr Yasko is that having  lot of data is not helpful if we do not have the knowledge to know what to do with this data in order to improve our health.

However, the science of genomics is rapidly evolving and new data is adding each month.  Considering that a Whole Genome Sequencing (WGS) is now about the same price as partial sequencing, paying for example $299 for a whole sequencing is a good choice.  Once you have all of your data, you can analyze only the parts you want - only the methylation-related SNPs if you want.  As the science of genomics is improving, you still have all of your genes data to do whatever new panel is available.

I guess her comment dates back a few years when a methylation panel could cost 100$, and a whole genome sequencing was around $1000 or $2000.  Now that a WGS is almost the same price as a very partial ( less than 1%) sequencing, it is a very interesting option.

I sure hope that, in some years, there will be many pathways that have been researched as much as the methylation pathway, and that we will have far more complete databases on the many SNPs.  For now, many SNPs are called 'VUS' or Variant of Uncertain Significance, meaning that we do not know yet what is their significance to the function or health of our body  ( see https://en.wikipedia.org/wiki/Variant_of_uncertain_significance ).   

[Quantum]

For those who have their genome sequencing done, I have discovered this week a free and interesting site where you can use tools to analyze your genome results:  https://geneticgenie.org/

They offer an overall analysis of your SNPs, with their GenVue Discovery application, at https://genvue.geneticgenie.org/

They also offer two panels, for now:  Methylation, and Detox.  The Methylation Panel contains information on every SNP tested in the panel.  The Detox panel is less developed in terms of interpretation info, only listing your results, but with a minimum of research, you will know what it means.


It is free to use but you can make a donation if you want.
The max size of the file you can upload there is 1 GB.  If you have a Whole Genome Sequencing, which is about 40 GB in size, the best file to upload there instead is a file with your SNPs only, that is, only the positions where your alleles are different from the reference genome ( that reference may be hg19/GRCh37 or hg38/GRCh38).  For example, my VCF file containing my SNPs is about 225 MB in size.  The VCF file format ( Variant Call Format) is only one kind of format, there are others that you may have your data in, and most are accepted by this website ( 23andMe, AncestryDNA, ...)

The general report ( Variant Report) is very interesting.  In the first tab, 'Genetic Conditions', it shows your SNPs for which there are expert reviews, meaning that the potential effects of those SNPs are better known. However, the fact of having such a variant does not necessarily mean one has or carries a condition or disease - it only means that you have a predisposition of developing this condition.  Since we have about 25 000 genes, you may have other genes that have blocked or compensate for the effect of a particular SNP, so you do not have this condition at all.
In the Variant Report, you also have a tab for SNPs about potential unusual drug responses to specific drugs.  You also have tabs where are listed your rare mutations of less than 1% frequency listed in ClinVar ( having a rare mutation may be more significant than having a common variant).  Being listed in ClinVar means that some information is known about these SNPs. There is also a tab for uncommon mutation of between 1% and 5% frequency, that are reported in ClinVar ( more frequent, but still relatively rare).
For each SNP list in your report, you have an abstract concerning this SNP, tags concerning its degree of pathogenicity and clinical significance, and links to many databases  ( LitVar, SNPedia, OMIM, dbSNP) having a specific page for this SNP, so you save a lot of time and easily find information on this on this specific SNP.

Doing the same report next year will produce a different report, with more data, and updated information.  In 5 years, it would be a quite different report, far more complete and descriptive ( information on more SNPs, more complete information on already known mutations, and so on).  I am very enthusiastic about this new developing science!

Let me know if you try the tools geneticgenie.org !
P.S.  I saw that Rollercoaster used this website for the reports he posted in this thread

[Prospero]

Rollercoaster, thank you for your reports, I have added the data in the first page.
Quantum, would you like to share your GeneticGenie reports with us?

[berlin1984]

They offer an overall analysis of your SNPs, with their GenVue Discovery application, at https://genvue.geneticgenie.org/

Wow nice. Thanks. I knew the panels and I had posted my results in the test result thread last year but I did not know GenVue, maybe it did not exist yet. Looks like a curated and nicer version of Promethease.

I found this for myself, very interesting:

Gene: BTD
Variant: c.1336G>C
(p.Asp446His)
rsID: rs13078881
Ref Allele: G
Alt Allele: C
Freq: 1.857% uncommon
Biotinidase deficiency, Autosomal recessive
Low clinical importance, pathogenic
I guess I need to buy a biotin supplement and see what it does. Note that I only have reduced activity, the full mutation is apparantly screened at birth even(?)
https://en.wikipedia.org/wiki/Biotinidase_deficiency
https://www.geneticlifehacks.com/genetics-of-biotin-deficiency/

The other one is:
Gene: AMPD1
Variant: c.133C>T
(p.Gln45Ter)
rsID: rs17602729
Ref Allele: G
Alt Allele: A
Freq: 3.8139% uncommon
Muscle AMP deaminase deficiency, Autosomal recessive
Low clinical importance, Likely pathogenic — Causes Adenosine Deaminase Deficiency in a recessive manner. Most of the time individuals do not report symptoms, but when symptoms do exist they to be post-exercise symptoms of muscle weakness, muscle pain, and getting tired more quickly.
https://www.geneticlifehacks.com/ampd1-deficiency/ says A/G: 50% reduction in AMP Deaminase function and recommends Creatine or Ribose.


Maybe more in other tabs, let's see :-)

[Quantum]

Rollercoaster, thank you for your reports, I have added the data in the first page.
Quantum, would you like to share your GeneticGenie reports with us?

Sure Prospero.
I will join the Methylation and Detox report with this post.
I have to figure out how to join the HTML report like Rollercoaster did, with a few hundred KB in size... when I try to upload it, the file is 4 MB , so there must be another way to upload it.

[Quantum]

Ok, I have found a way to reduce the Variant Reports files size. I use the 'print" function of the browser and save it as a PDF.  It keeps the links clickable but the report loses a little color in the process.   


Here is my 'Genetic Conditions' report, which is a small file.  Also, my 'Rare Mutations' report, which is quite large, at 2 MB, because it is done from a WGS ( Whole Genome Sequencing).  I have over 180 rare mutations listed, compared to about 20 in rollercoaster's report ( Done from a partial sequencing, so less SNP listed).

Take note that I do not have all of these diseases   You have to get use to read gene reports as 'potential' to have certain conditions or not having them. We have around 25000 genes, and it is a very complex machinery, so even if I have a homozygous rare mutation for a terrible syndrome that could have caused me mental retardation, short stature, infertility, and so on, it was only a potential phenotype.  This 'bad gene' may have been blocked by another gene or a combination of other genes I have.  So, before we can find what causes POIS symptoms, a lot of work will have to be done.  We have to see what mutation is really manifesting as a phenotype in our body.  All mutations are not clinically significant, and not all clinically significant mutations manifest as an actual clinical problem.  The genome data analysis will progress in the years and decades to come, but for now, caution is advised in interpreting genetic results.


An interesting way to find what genes are linked to POIS would be to do a GWAS ( Genome-Wide Association Study).  This means you run the genome of a group of POIS sufferers against the genome of a reference population without POIS, and find what mutations and SNPs the POIS sufferers have in common that the general population does not have.

This is the kind of test that was proposed by BegonePOIS, earlier in this thread.  However, he did not answer yet my question about how many genome files from POIS sufferers he would need to run this kind of test and have significant results. But clearly, the more genome sequencing files we have from more different POIS sufferers, the better it would be.


 

[Quantum]

They offer an overall analysis of your SNPs, with their GenVue Discovery application, at https://genvue.geneticgenie.org/

Wow nice. Thanks. I knew the panels and I had posted my results in the test result thread last year but I did not know GenVue, maybe it did not exist yet. Looks like a curated and nicer version of Promethease.

I found this for myself, very interesting:

Gene: BTD
Variant: c.1336G>C
(p.Asp446His)
rsID: rs13078881
Ref Allele: G
Alt Allele: C
Freq: 1.857% uncommon
Biotinidase deficiency, Autosomal recessive
Low clinical importance, pathogenic
I guess I need to buy a biotin supplement and see what it does. Note that I only have reduced activity, the full mutation is apparantly screened at birth even(?)
https://en.wikipedia.org/wiki/Biotinidase_deficiency
https://www.geneticlifehacks.com/genetics-of-biotin-deficiency/

The other one is:
Gene: AMPD1
Variant: c.133C>T
(p.Gln45Ter)
rsID: rs17602729
Ref Allele: G
Alt Allele: A
Freq: 3.8139% uncommon
Muscle AMP deaminase deficiency, Autosomal recessive
Low clinical importance, Likely pathogenic — Causes Adenosine Deaminase Deficiency in a recessive manner. Most of the time individuals do not report symptoms, but when symptoms do exist they to be post-exercise symptoms of muscle weakness, muscle pain, and getting tired more quickly.
https://www.geneticlifehacks.com/ampd1-deficiency/ says A/G: 50% reduction in AMP Deaminase function and recommends Creatine or Ribose.


Maybe more in other tabs, let's see :-)

Very interesting.  Be sure to update us about these 'genomic supplements' and their effect on your health.
In my case, I already knew about Vitamin D and have taken 2000 ui daily for over a year now, and my blood level are ok now ( it sure help me get some more energy and resistance to infections and inflammation).
In my data, I also found SNPs suggesting I should take more B12, more vitamin A, and more choline. Since last month, I have taken what I call my 'genomic vitamins' daily, and I looks like it gave me maybe 5% to 10% more energy, which is significant..  As a bonus, my ever-present canker sores seem to heal faster and be far less painful.  It is too soon to conclude, but so far it is positive.   

 

[drop247]

Berlin,
I have the same mutations as you. What are the odds of us both having two uncommon mutations I wonder? It could be a lead to investigate further.

Gene: BTD
Variant: c.1336G>C
(p.Asp446His)
rsID: rs13078881
Ref Allele: G
Alt Allele: C
Freq: 1.857%uncommon
CADD: 23.3

ClinVar Submissions (15)

    Biotinidase deficiency, Autosomal recessive

Hetero
CG

Gene: AMPD1
Variant: c.133C>T
(p.Gln45Ter)
rsID: rs17602729
Ref Allele: G
Alt Allele: A
Freq: 3.8139%uncommon
CADD: 36

ClinVar Submissions (6)

    Muscle AMP deaminase deficiency, Autosomal recessive

[berlin1984]

Berlin,
I have the same mutations as you. What are the odds of us both having two uncommon mutations I wonder? It could be a lead to investigate further.

Nice! 

Although they might not be so uncommon in white/caucasian (assuming you are, sorry if this is incorrect)

Did you also see my mutations here: https://poiscenter.com/forums/index.php?topic=2684.msg42120#msg42120 ?

[Progecitor]

They offer an overall analysis of your SNPs, with their GenVue Discovery application, at https://genvue.geneticgenie.org/

Wow nice. Thanks. I knew the panels and I had posted my results in the test result thread last year but I did not know GenVue, maybe it did not exist yet. Looks like a curated and nicer version of Promethease.

I found this for myself, very interesting:

Gene: BTD
Variant: c.1336G>C
(p.Asp446His)
rsID: rs13078881
Ref Allele: G
Alt Allele: C
Freq: 1.857% uncommon
Biotinidase deficiency, Autosomal recessive
Low clinical importance, pathogenic
I guess I need to buy a biotin supplement and see what it does. Note that I only have reduced activity, the full mutation is apparantly screened at birth even(?)
https://en.wikipedia.org/wiki/Biotinidase_deficiency
https://www.geneticlifehacks.com/genetics-of-biotin-deficiency/

The other one is:
Gene: AMPD1
Variant: c.133C>T
(p.Gln45Ter)
rsID: rs17602729
Ref Allele: G
Alt Allele: A
Freq: 3.8139% uncommon
Muscle AMP deaminase deficiency, Autosomal recessive
Low clinical importance, Likely pathogenic — Causes Adenosine Deaminase Deficiency in a recessive manner. Most of the time individuals do not report symptoms, but when symptoms do exist they to be post-exercise symptoms of muscle weakness, muscle pain, and getting tired more quickly.
https://www.geneticlifehacks.com/ampd1-deficiency/ says A/G: 50% reduction in AMP Deaminase function and recommends Creatine or Ribose.


Maybe more in other tabs, let's see :-)

I currently don't have the funds to do genetic profiling, but I have tried biotin before. As I mentioned it induced an acute POIS attack for about 1-2 days as if I actually had an O event. That is why I wanted to know if others had a similar experience. So if you take biotin be prepared for the worst even though a biotinidase deficiency would suggest that biotin supplementation could help you a lot. The amount I had taken couldn't be considered much as it was only a 300 mcg capsule. As I remember one to two hours after consumption I developed quite severe bloodshot eyes and felt generally unwell. Be sure to keep some saffron at hand if this happens as it helped me reduce the effect.
When I first took biotin I was at the beginning of acute POIS and the result was quite severe, however at another time I took it at the beginning of the chronic phase and it hit me less severely then. I planned to do some more tinkering with biotin as I think I noticed that the urine completely lost its burning quality at the time and my theory was that biotin only shifts POIS from the urine to the blood by preventing the excretion of the causative compound. Given your genetic results now I am not so sure if it is only a modifier of POIS, but be sure to report if you experience something similar. At best it may really help in your case, however our medication profile seems to align a lot and it has to be more than coincidence.

[drop247]

Nice! 

Although they might not be so uncommon in white/caucasian (assuming you are, sorry if this is incorrect)

Did you also see my mutations here: https://poiscenter.com/forums/index.php?topic=2684.msg42120#msg42120 ?

Yes, I'm Caucasian. I checked my histamine degradation mutations and I do have the same reduced HNMT mutation as you. I do not have the reduced DAO production though. How are your methylation cycle genes? I'm heterozygous on one of them that says results in a 40% reduction in methylation.

So in summary on top of the Biotin and AMP deficiency genes I also have the following histamine degradation deficiency genes:

HNMT:
rs1050891 A/A: reduced breakdown of histamine compared to G/G

Methylation:
rs1801133 A/G: one copy of MTHFR C677T allele (heterozygous), decreased by 40%

[Prospero]

My data doesn't include the two mutations mentioned by berlin and drop.
Under the "genetic conditions" category, there are mainly my MTHFR variants, a SERPINA1 variant (may induce alpha1 antitrypsin deficiency), the same CCDC170 variant as Quantum (estrogen resistance) and LCT;MCM6 double mutation (lactase persistence).
"Other risks" include variants for MT-ND1, BCKDHA, UGT1A1, ACTN3, PCSK9, DHCR7, DGUOK, HEXA, COL5A1, HTT, SLC6A20, EHBP1, DCAF17, FGFR4 and CCL2.

@ Quantum, thank you for your reports, I'll add the data soon.

[drop247]

the same CCDC170 variant as Quantum (estrogen resistance) and LCT;MCM6 double mutation (lactase persistence).

I have these too. Though they seem like very common variants.

[berlin1984]

Berlin,
I have the same mutations as you. What are the odds of us both having two uncommon mutations I wonder? It could be a lead to investigate further.
Gene: AMPD1
Variant: c.133C>T
(p.Gln45Ter)
rsID: rs17602729
Ref Allele: G
Alt Allele: A
Freq: 3.8139%uncommon
CADD: 36
Muscle AMP deaminase deficiency, Autosomal recessive

Found a great blog post explaining how this can lead to daytime sleepiness.
https://medium.com/@atomoton/mutants-among-us-the-unexpected-effects-of-a-mutation-in-ampd1-b4f99c911377

[drop247]

Berlin,
I have the same mutations as you. What are the odds of us both having two uncommon mutations I wonder? It could be a lead to investigate further.
Gene: AMPD1
Variant: c.133C>T
(p.Gln45Ter)
rsID: rs17602729
Ref Allele: G
Alt Allele: A
Freq: 3.8139%uncommon
CADD: 36
Muscle AMP deaminase deficiency, Autosomal recessive

Found a great blog post explaining how this can lead to daytime sleepiness.
https://medium.com/@atomoton/mutants-among-us-the-unexpected-effects-of-a-mutation-in-ampd1-b4f99c911377

Thanks for the link. I will experiment with caffeine like it suggests. I don't tolerate coffee probably because of the histamine but I have caffeine pills. I've also read Ribose is used to treat AMPD1 so I've ordered that and will let you know if I have any positive results with it or caffeine pills.

[berlin1984]

Are you sure you have coffee problen because of histamine?
Because we have the same genes there, maybe your problem is somewhere else with coffee, e.g. this slow/fast metabolizer of caffeeine?
(But: you might have more histamine load because of "wrong" gut bacteria or diet)

I'm trying creatine again, used to take it before but stopped. It's supposed to help too.

[drop247]

Nope I'm not sure at all. I go back and forth on whether my issues are histamine related or not.