23andme & Chronic insomnia and family history of psychiatric/CNS disorders

[futuritycarpaccio]

@ppodhajski really good catch on the GPX's. Especially the GPX1, 4.6% frequency, maybe it's one of the problems!
It's also connected to seizure susceptibility and oxidative stress. I will buy selenium today.

 

[ppodhajski]

Sort of, and sort of not.

Proper genetic diseases are pretty much only caused by rare SNPs (due to killing people off or making reproduction unlikely), so frequency can be used to help put common SNPs into perspective. If half the planet has the "+" allele, it can safely be assumed to either be doing very little, or that the body is very good at dealing with it.

Even looking at very low frequencies, everyone has quite a few SNPs at or under 1%, and having a few under 0.1% is pretty common as well. My rare SNP program pulls out about 100 SNPs on average at 1% prevalence or less for everyone's 23andMe results. And that's not looking at sex chromosomes or mitochondrial DNA. It also isn't including SNPs with no prevalence data, as happens with pathogenic SNPs and SNPs which have only recently been labeled. So for approximately every 10,000 SNPs from 23andME, 1 is going to be very rare.

Also consider that 23andMe is looking at less than 1 million SNPs, out of 3 billion possible SNPs. So that would suggest that about 300,000 SNPs on every person's genome are going to be very rare. While a couple of those might actually be having a significant impact, simple rarity isn't enough to distinguish which ones they are, or if any are. And how likely is it that 23andMe is getting the most relevant very rare SNPs, when the vast majority of very rare SNPs aren't tested by 23andMe?

And another consideration is that many genes will be completely functional when heterozygous for a mutation, even if that mutation is deadly when homozygous.

So I think rarity provides a starting point to look for problems, and it's a way to filter out a lot of pretty harmless variations. But rarity is very common and is not an indication of problems by itself.

Valentijn, I am coming from a very different place in looking at this and it has yielded results so I think you have to let go of your ideas for a moment to see where I am coming from.

First, I only look at epigenetic genes, the genes that are effected by environment, like food, stress, etc. I look at gene SNPS, like COMT SNPs that lower the function of the enzyme. While this is not catastrophic on its own, combine it with MAOA and MAOB SNPs that also slow the degradation of catecholamines and we have issues (like I had; anxiety, IBS-D, Sebbhorreic Dermatitis) and add on that GPX or SOD SNPs and we have even more serious issues.

Yes, the frequency is sometimes important, but this is why I see this as more of an art than a science. What I do find, is that USUALLY, a lower frequency (occurrence) of a SNP in some epigenetic gene will LIKLEY be associated with some disease. Again, it is not the single SNP, but all the SNPs together in the epigenetic pathway that I look at.

However, the risk allele will ALWAYS result in a reduced function of the enzyme no matter what the frequency in the population. This is hugely important when it comes to epigenetics.

For example, here is the distribution of the SNPs associated with PEMT rs4646406 where the T (-) allele leads to lower enzyme function:

You see the TT (-/-) frequency is much higher in Mexicans. What that means is that more Mexicans have a harder time converting SAMe to phosphaditlecholine. This is why Mexicans have a higher rate of heart disease, orofacial clefts and endometrial carcinoma.
http://www.ncbi.nlm.nih.gov/pubmed/19737740
http://www.hindawi.com/journals/isrn/2012/178051/

So in fact, it is not rare in to see PEMT (-/-) in Mexicans, so therefore we see a higher rate of disorders associated with that SNP in Mexicans than in Northern Europeans.

This is so simple it is killing me that few people see it.

Thanks for your dialogue, I appreciate it.

 

[Valentijn]

However, the risk allele will ALWAYS result in a reduced function of the enzyme no matter what the frequency in the population. This is hugely important when it comes to epigenetics.

Actually no, it won't always result in a reduction.

Studies are usually looking at correlations with diseases or blood results (risk factors) rather than actual function of the gene. Or even worse, they're making conclusions based on correlation with personality traits. They do this by seeing if a specific allele or genotype is more frequent in a group which has a disease, has a higher or lower lab result (not necessarily even abnormal), or has a supposed personality feature.

When they do this, they are finding that one allele or genotype is slightly more common in one group than the other. This means that the supposed risk allele is still extremely common in the non-risk groups. Hence it often results in completely normal functioning, even if we take it at face value that the effect size and significance are valid and appropriately calculated.

And even when looking at actual expressed gene functioning, there is usually a large overlap between the expressed gene functioning for the "risk" alleles and the non-risk alleles. Hence a lot of people with the risk allele have normal gene functioning, and some people with the non-risk allele have abnormal functioning.

Another huge problem is that these studies use very high p-values (0.05, 0.01), frequently without bothering to correct the p-value to account for the huge number of SNPs. This seems to be especially prevalent in the more social (personality, addiction, etc) research, presumably due to the researchers being incapable of comprehending even the basics of statistics, and/or being unable to convince a statistician to spin their results in the desired manner.

And to make things even more amusing, research involving the SNPs with a very small effect size will quite often report that the more common allele is the "risky" one. This has happened in most of the CFS SNP research thus far, due to high p-values, excessive enthusiasm over tiny effect sizes, small patient groups, poor disease definition, and failure to correct for the odds of getting a false-positive when looking at hundreds of SNPs at the same time. Hence pretty much everyone in the world is supposedly at increased risk of getting CFS - except for ME/SEID patients from this forum, who generally have results which are the opposite of those studies.

At the very least, before taking any findings of risk seriously in a study, I'd expect to see:

1. A large group of patients - this reduces the chance of false-positives
2. Proper correction for the number of SNPs studied, to account for the increased likelihood of false-positives
3. A decent effect size for studies looking at correlation rather than actual gene function - an increased risk factor from 0.1% to 0.2% for developing a disease is not of any practical use, except possibly as a foundation for further research to look for additional necessary factors
4. Replication with a completely different group of patients, again to ensure this is a consistent finding and not a random false-positive

Unfortunately, this sort of SNP research is relatively rare. There is some solid research out there, but there's also a ton of dodgy stuff from which no conclusion can be drawn.

 

[ppodhajski]

First, again, thanks for the dialogue, there are few people who put in the time to write so much on their views so clearly.

Actually no, it won't always result in a reduction.

Actually, yes, it will. Diet or other environmental effects can change the expression, but keeping all things the same for another person with a normal SNPs, the person with the risk allele will show reduced activity. This is why the look at genes, to know which ones are not functioning properly.

For more on this see some of Dr. Steven Zeisel videos on the subject and why nutritional research or genetic research, when done in a vacuum, will never yield results.

Studies are usually looking at correlations with diseases or blood results (risk factors) rather than actual function of the gene. Or even worse, they're making conclusions based on correlation with personality traits. They do this by seeing if a specific allele or genotype is more frequent in a group which has a disease, has a higher or lower lab result (not necessarily even abnormal), or has a supposed personality feature.

When they do this, they are finding that one allele or genotype is slightly more common in one group than the other. This means that the supposed risk allele is still extremely common in the non-risk groups. Hence it often results in completely normal functioning, even if we take it at face value that the effect size and significance are valid and appropriately calculated.

And even when looking at actual expressed gene functioning, there is usually a large overlap between the expressed gene functioning for the "risk" alleles and the non-risk alleles. Hence a lot of people with the risk allele have normal gene functioning, and some people with the non-risk allele have abnormal functioning.

The one thing you are missing is the reason WHY a gene express or not. When you understand that you will understand where I am coming from. Take the BRCA1 SNP for example. Women who have this do not always get cancer even though it is high risk. So what is it that increases the risk. or in other words, what is it that makes the gene "express".

Another huge problem is that these studies use very high p-values (0.05, 0.01), frequently without bothering to correct the p-value to account for the huge number of SNPs. This seems to be especially prevalent in the more social (personality, addiction, etc) research, presumably due to the researchers being incapable of comprehending even the basics of statistics, and/or being unable to convince a statistician to spin their results in the desired manner.

And to make things even more amusing, research involving the SNPs with a very small effect size will quite often report that the more common allele is the "risky" one. This has happened in most of the CFS SNP research thus far, due to high p-values, excessive enthusiasm over tiny effect sizes, small patient groups, poor disease definition, and failure to correct for the odds of getting a false-positive when looking at hundreds of SNPs at the same time. Hence pretty much everyone in the world is supposedly at increased risk of getting CFS - except for ME/SEID patients from this forum, who generally have results which are the opposite of those studies.

At the very least, before taking any findings of risk seriously in a study, I'd expect to see:

1. A large group of patients - this reduces the chance of false-positives
2. Proper correction for the number of SNPs studied, to account for the increased likelihood of false-positives
3. A decent effect size for studies looking at correlation rather than actual gene function - an increased risk factor from 0.1% to 0.2% for developing a disease is not of any practical use, except possibly as a foundation for further research to look for additional necessary factors
4. Replication with a completely different group of patients, again to ensure this is a consistent finding and not a random false-positive

Unfortunately, this sort of SNP research is relatively rare. There is some solid research out there, but there's also a ton of dodgy stuff from which no conclusion can be drawn.

Again, this research is useless because as long as it does not account for environmental factors they will continue to get "noise".

 

[Valentijn]

Actually, yes, it will. Diet or other environmental effects can change the expression, but keeping all things the same for another person with a normal SNPs, the person with the risk allele will show reduced activity. This is why the look at genes, to know which ones are not functioning properly.

Is this your private theory, or there some substantiation of it somewhere? Because I have never seen any research guaranteeing that these SNPs will start to have an extreme effect when combined with certain environmental influences. Except to the extent that certain environmental exposures literally make everyone sick

The one thing you are missing is the reason WHY a gene express or not. When you understand that you will understand where I am coming from. Take the BRCA1 SNP for example. Women who have this do not always get cancer even though it is high risk. So what is it that increases the risk. or in other words, what is it that makes the gene "express".

I think you're mistaken in assuming that these SNPs are 100% responsible for disease in any situation, even when combined with supposed environmental triggers. Additionally, there was some research recently which contradicts your theory, at least in the specific case of cancers. Basically the cancer is caused by mutations occurring in the cancerous tissues, and they were found to be random, rather than triggered by environmental factors.

Mutation does happen constantly ... basically cytosine (C), one of the 4 bases of DNA and RNA, has a tendency to degrade into a different nucleobase. This is usually harmless, and rarely transmitted to offspring, as it's limited to the tissue where it happens and doesn't spread. But certain unfortunate local spontaneous mutations can also result in cancerous tissue, and the current data seems to indicate that's where the primary responsibility lies for many cancers.

Again, this research is useless because as long as it does not account for environmental factors they will continue to get "noise".

That's your opinion. But many studies do take various factors into account. Until environmental factors can be shown to have these dramatic effects on otherwise normal or nearly-normal SNPs, it remains broad speculation.

 

[ppodhajski]

Is this your private theory, or there some substantiation of it somewhere? Because I have never seen any research guaranteeing that these SNPs will start to have an extreme effect when combined with certain environmental influences. Except to the extent that certain environmental exposures literally make everyone sick

I think you're mistaken in assuming that these SNPs are 100% responsible for disease in any situation, even when combined with supposed environmental triggers. Additionally, there was some research recently which contradicts your theory, at least in the specific case of cancers. Basically the cancer is caused by mutations occurring in the cancerous tissues, and they were found to be random, rather than triggered by environmental factors.

Mutation does happen constantly ... basically cytosine (C), one of the 4 bases of DNA and RNA, has a tendency to degrade into a different nucleobase. This is usually harmless, and rarely transmitted to offspring, as it's limited to the tissue where it happens and doesn't spread. But certain unfortunate local spontaneous mutations can also result in cancerous tissue, and the current data seems to indicate that's where the primary responsibility lies for many cancers.

That's your opinion. But many studies do take various factors into account. Until environmental factors can be shown to have these dramatic effects on otherwise normal or nearly-normal SNPs, it remains broad speculation.

I DID NOT SAY "these SNPs are 100% responsible for disease in any situation". I DO NOT SAY THAT.

Do you get me? I did not say that. Show me where I wrote that. Please. Do you see how your brain is misreading what I write?

And I want you to show me some research now that backs this up: "Additionally, there was some research recently which contradicts your theory, at least in the specific case of cancers. Basically the cancer is caused by mutations occurring in the cancerous tissues, and they were found to be random, rather than triggered by environmental factors."

 

[Valentijn]

I DID NOT SAY "these SNPs are 100% responsible for disease in any situation". I DO NOT SAY THAT.

Do you get me? I did not say that. Show me where I wrote that. Please. Do you see how your brain is misreading what I write?

Sure:

Actually no, it won't always result in a reduction.

Actually, yes, it will.

And I want you to show me some research now that backs this up: "Additionally, there was some research recently which contradicts your theory, at least in the specific case of cancers. Basically the cancer is caused by mutations occurring in the cancerous tissues, and they were found to be random, rather than triggered by environmental factors."

http://www.sciencemag.org/content/347/6217/78.abstract

 

[ppodhajski]

Sure:

http://www.sciencemag.org/content/347/6217/78.abstract

Ha! Perfect (bad) study. You are totally misinterpreting what they said.They in NO WAY said that these cancers are not environmental. And yet you show me ONE study where I showed you dozens that show evidence that oxidative stress causes the symptoms of ME/CFS.

http://www.bbc.com/news/magazine-30786970
The researchers say they've calculated that two thirds (65%) of "the differences in cancer risk among different tissues" is down to cell division gone wrong - "bad luck". Now many media reports have simply concluded that this means that two thirds of cancer cases are just the result of random haywire cell division. That's not correct.

But on the other hand, a lot of people aren't quite sure exactly what the researchers mean. Statistical and scientific experts who have been blogging about the misreading of the research don't all agree about what the 65% figure refers to.

The most likely explanation seems to be that the researchers were referring to the correlation between cell divisions in different types of tissue, and the tendency of those tissues to develop cancer.

 

[Gondwanaland]

For more on this see some of Dr. Steven Zeisel videos on the subject and why nutritional research or genetic research, when done in a vacuum, will never yield results.

If you start a thread please by all means include this video in the opening post. I am loving it

 

[ppodhajski]

If you start a thread please by all means include this video in the opening post. I am loving it

Yes, he is a genius in my book, as is his whole department at UNC.

 

[futuritycarpaccio]

Today and the next 2 days will be exams days (before I start supplementing). Half of this will be paid in advance from my pocket as I wait to find a caring doctor who will prescribe me many of these...

Today:
Plasma:
- 11 Desoxicortisol
- Cortisol
- DHEA
- Pregnenolone
- Progesterone
- ACTH
- DHT
- 3adiolG
- Zinc
- Copper
- Vitamin D 25 OH
- Total Testosterone
- Free Testosterone
- Prolactin
- Albumin
- SHGB

Urine:
- Catecholamines

Saliva:
- DHEA-S one sample
- Cortisol saliva (16.30-17; 23.30-00.15;8-9am; 12.30-13.15)

Tomorrow:
- Cortisol 24 hour urine

Day after:
- Cortisol suppression test with Dexa


I'm eager for the results, especially for bioavailable test, cortisol in saliva, vitamin D and zinc/copper. I'm also eager to test Dexa. I have decided not to test RT3 and T3. What's the point?! It would cost 60 or 80€ and I already know by my over range TSH that I'm hypo or subclinical hypo. Nothing new out of that exam.

Unfortunately my results will take around a month....this south of portugal is the end of the world!

I feel this time I will find out what is wrong with me after many years of misterious suffering and "everything is normal with you" attitudes by doctors and even close people.

 

[ppodhajski]

Today and the next 2 days will be exams days (before I start supplementing). Half of this will be paid in advance from my pocket as I wait to find a caring doctor who will prescribe me many of these...

I feel this time I will find out what is wrong with me after many years of misterious suffering and "everything is normal with you" attitudes by doctors and even close people.

Very cool. I will reply again with my guesses on your results.

 

[Hip]

Hi ppodhajski

Just reading your posts, and trying to follow your ideas, which seem interesting.

If I have understood your approach correctly, what you are doing is this:

(1) Determining which of your SNPs are the rarest, using the promethease.com report, which I understand covers around 20,000 out of the nearly 1 million SNPs in your 23andme raw data file, and provides info on how common or rare an SNP is in the general population.

(2) Then on the assumption that the genes which contain the rarest SNPs may well be problematic genes that are functioning under par, you use the data provided on the www.uniprot.org website to learn, for each of your genes that contains a rare SNP, which cofactors are required by that gene to function.

(3) You then take dietary supplements to supply those cofactors, with the idea that this will support and improve the performance of these possibly problematic genes.

Is that an accurate summary of what your approach entails?



I have some questions on your approach, if I may:

• In the Promethease report, which I understand details around 20,000 SNPs, how many of those 20,000 are rare SNPs? I just want to get an idea of how many rare SNPs there might be in this report. Obviously it depends on your definition of rare (eg, 1% of the population, 5%, etc). I am assuming that there may be hundreds of rare SNP, and if that is the case, how do you decide which ones to try to support using dietary supplements? Is this based on hunches, choosing genes to support which you think might make a positive impact? Or do you focus on certain types of gene, such as those involved in making neurotransmitters, or those that are involved in the immune system?

• In your case, and in the case of the other people you used your approach on, how many rare SNP-containing genes did you target, and how many different supplements was it necessary to take in order to support those rare SNP-containing genes you targeted?

• You said that "It is not useful to me to waste time looking at the receptors since we cannot change them." Could you explain this a bit more.

• You mention that you only focus on "epigenetic genes". Can you please explain what you mean by this. I assumed that the expression of all genes can be controlled via epigenetic mechanisms, such as methylation and histone acetalization. Aren't all genes epigenetic genes?

 

[ppodhajski]

Hi ppodhajski

Just reading your posts, and trying to follow your ideas, which seem interesting.

If I have understood your approach correctly, what you are doing is this:

(1) Determining which of your SNPs are the rarest, using the promethease.com report, which I understand covers around 20,000 out of the nearly 1 million SNPs in your 23andme raw data file, and provides info on how common or rare an SNP is in the general population.

Close. I do not just look for the rarest SNPs. I look at SNPs in the Methionine, Transulfuration, and Catecholamine pathways and a few others, like the Krebs cycle and Glucose Pathway. The rarity is just a way I use to know if a gene in those pathways are fast or slow. I do not treat all of the SNPs, but they give me a clue to the "flow" of this complex of pathways. That is the best way my mind can put it.

I do not see the a SNP as a problem on its own, but the combination of SNPs in all these pathways is just a way for me to see the way people express disease and what can help them.

(2) Then on the assumption that the genes which contain the rarest SNPs may well be problematic genes that are functioning under par, you use the data provided on the www.uniprot.org website to learn, for each of your genes that contains a rare SNP, which cofactors are required by that gene to function.

(3) You then take dietary supplements to supply those cofactors, with the idea that this will support and improve the performance of these possibly problematic genes.

Is that an accurate summary of what your approach entails?

Yes, the rest is correct.

I have some questions on your approach, if I may:

• In the Promethease report, which I understand details around 20,000 SNPs, how many of those 20,000 are rare SNPs? I just want to get an idea of how many rare SNPs there might be in this report. Obviously it depends on your definition of rare (eg, 1% of the population, 5%, etc). I am assuming that there may be hundreds of rare SNP, and if that is the case, how do you decide which ones to try to support using dietary supplements? Is this based on hunches, choosing genes to support which you think might make a positive impact? Or do you focus on certain types of gene, such as those involved in making neurotransmitters, or those that are involved in the immune system?

Yes, I folcus on genes that effect methylation and de-methylation. I have about 200 SNPs I look at but will only treat four or five of them with supplements and a lot of them are the same supplements. I will list all the SNPs at the end of this post.

My self personally, with a change in diet a lot of days I take nothing. I take supplements if I feel symptoms or as preventives. For example, if I know I am going to eat dinner out I might take some FMN (B2) to help me process dietary amines.

[

• In your case, and in the case of the other people you used your approach on, how many rare SNP-containing genes did you target, and how many different supplements was it necessary to take in order to support those rare SNP-containing genes you targeted?

Again, rarity is not the issue. I am afraid that was misinterpreted by another member. I take four supplements mostly. Biotin (BTD), FMN (MAOA, MAOB, MTRR, MTHFR), Magnesium (COMT) and P5P (GAD1). I also changed my environment. Low amine, low protein, low glutamate, low stress. The only one I take everyday is Biotin.

I also take on occasion Optizinc, molybedenum/thiamine, manganese, and selenium. But I try to get these from foods.

Note that I NEVER take the products of these pathways. Doing so creates issues like when the give levdopa to parkinsons patients.

[

• You said that "It is not useful to me to waste time looking at the receptors since we cannot change them." Could you explain this a bit more.

I look at the receptor SNPs because that gives me a way to gauge the importance of the donator SNP. For example, my GAD1 SNPs are bad, leaving a lot of glutamate around and making me low in GABA. My GABA receptor SNPs (GABRA) are very bad as well, causing me to NEED more GABA. Knowing that, I see I might need more P5P to help me create more GABA than people who do not have as bad GABA receptor SNPs.

[

• You mention that you only focus on "epigenetic genes". Can you please explain what you mean by this. I assumed that the expression of all genes can be controlled via epigenetic mechanisms, such as methylation and histone acetalization. Aren't all genes epigenetic genes?

All the genes I look at have some influence in DNA methylation or de-methylation.
For example, MAO;
Histone H3 Lysine 4 Demethylation Is a Target of Nonselective Antidepressive Medications
http://www.sciencedirect.com/science/article/pii/S0014579305003376

Thank you for the detailed questions!

These are the SNPs I look at:


MTHFR
rs1801133
rs1801131
rs4846048
rs1476413
rs6676300
rs4846049
MTHFD1
rs2295639
rs10498514
rs2236225
rs2236224
MTHFD1L
rs803422
rs6922269
MTHFS
rs6495446
BHMT
rs651852
rs3733890
rs567754
PEMT
rs7946
rs4646406
MTRR
rs1801394
rs3776467
GCH1
rs4411417
rs752688
rs8007267
PTS
rs3819331
TPH2
rs4570625
rs17110690
rs4565946
rs10506645
rs1487278
rs11179002
TYR
rs1393350
rs1847134
rs1799989
TPO
rs1514687
rs732609
TH
rs6356
DDC
rs3735273
rs1451375
rs921451
rs2329340
rs11974297
rs1451371
DBH
rs77905
rs1108580
rs2007153
rs1611115
rs2283123
MAOA
rs909525
MAOB
rs2283729
rs1799836
COMT
rs4633
rs4680
rs165722
GAD1
rs769407
rs3791878
rs3791851
rs12185692
rs3828275
rs2241165
rs3749034
GABRA2
rs11503014
rs279845
rs279836
rs279858
rs279826
GABRA3
rs750841
GABRA4
rs17599416
SUOX
rs10876864
SOD1
rs2070424
rs1041740
SOD2
rs2758331
rs4880
SOD3
rs2536512
rs1799895
GPX1
rs1800668
rs1050450
GPX2
rs2071566
GPX3
rs3828599
rs8177447
rs8177404
rs8177406
GPX4
rs757228
rs2074451
GSTP1
rs1695
rs1871042
TTPA
rs35916840
CBS
rs1801181
rs2851391
rs4920037
rs234706
rs234709
rs6586282
rs234715
CTH
rs1021737
DAO
rs4623951
rs2070586
rs3741775
rs1935062
rs3916967
DAOA
rs3916967
rs2391191
rs3918341
rs947267
HNMT
rs1050891
FADS1
rs174549
rs174550
rs174546
rs174547
rs174548
rs174556
FADS2
rs482548
rs174575
rs174570
rs498793
rs1535
rs174576
GCK
rs730497
rs1799884
G6PC2
rs560887
GPT
rs1063739
PC
rs28940589
MCM6
rs4988235
rs182549
LCT
rs2322659
BTD
rs13078881
rs7651039
BCMO1
rs12934922
rs7501331

 

[Hip]

@ppodhajski

Thanks for that explanation, and thanks very much for that list of genes you think are important to look at.

Close. I do not just look for the rarest SNPs. I look at SNPs in the Methionine, Transulfuration, and Catecholamine pathways and a few others, like the Krebs cycle and Glucose Pathway. The rarity is just a way I use to know if a gene in those pathways are fast or slow.

OK, so you are saying that you have certain genetic areas that you specifically focus on, such as the genes involved in the following pathways:

methionine
transsulfuration
catecholamine
Krebs cycle
glucose
and the genes that effect methylation and de-methylation

Then you look for genes in these specific pathways that contain rare SNPs, as this can be a good clue to the genes that may be functioning slower or more weakly than the genes found in the general population.

I like the general concept of this method of using SNP rarity to highlight genes that may be functioning slower than normal.



Presumably the list of genes that are important to look at will vary a bit from one disease to the next. For example, if we consider neurological or psychiatric conditions, the genes important in these type of diseases might be different from say the genes involved in say autoimmune diseases, or cancer.

 

[ppodhajski]

@ppodhajski

Presumably the list of genes that are important to look at will vary a bit from one disease to the next. For example, if we consider neurological or psychiatric conditions, the genes important in these type of diseases might be different from say the genes involved in say autoimmune diseases, or cancer.

This is the most important part of what I am seeing. That these genes I look at will cause expression of disease like cancer, autoimmune, etc based on those other gene SNPs.

So for example, if a woman has BRCA1 SNPs and her epigentic pathway is in balance she will not get breast cancer. When it is out of balance she will get breast cancer. Another woman with a high risk CHEK2 SNP and not BRCA1 will get endometial cancer instead.

I see diseases as traits that get expressed when this pathway is over burdened. You will see that in this epigentic pathway that either oxidative stress is created or removed. It imbalance here that causes disease.

You should also be away is that the way they try to kill cancer is with drugs like methotrexate which blocks the folate cycle by inhibiting the DHFR enzyme.

 

[Hip]

@ppodhajski
Can I just confirm that when you say "epigenetic pathway", what you mean is the "methylation pathway". In other words, the pathway that people try to optimize by the methylation protocol.

 

[ppodhajski]

@ppodhajski
Can I just confirm that when you say "epigentic pathway", what you mean is the "methylation pathway". In other words, the pathway that people try to optimize by the methylation protocol.

Yes, kind of, I am doing everything I can to change that term becasue I feel like it is missing importnat pathways, like the glucose pathway. Methylation just leaves people focused on "methyls" and I think most people has a large misunderstanding about the role of methyl groups in the cycle.

I feel the term epigenetic fits better since it is also encompasses the heritability of disease.

 

[Hip]

People may find it a bit confusing if you use the term "epigenetic pathway", when what you really mean is "the set of genes I am interested in", ie, the genes you listed for me above.

I assumed — and I think other people will too — that when you used this phrase "epigenetic pathway" that you were referring to some specific area of science that goes by that name.

 

[ppodhajski]

People may find it a bit confusing if you use the term "epigenetic pathway", when what you really mean is "the set of genes I am interested in", ie, the genes you listed for me above.

I assumed — and I think other people will too — that when you used this phrase "epigenetic pathway" that you were referring to some specific area of science that goes by that name.

I am referring to a specific area of science that goes by that name:
http://genesdev.cshlp.org/content/23/7/781.full