Phoenix Rising: The Gift That Keeps on Giving All Year Long
This holiday season Jody Smith turns her eyes to the people of Phoenix Rising and gives thanks for you all ...
Discuss the article on the Forums.

Summarise further report pros and cons after 23andme?

Discussion in 'Genetic Testing and SNPs' started by Jenny TipsforME, Apr 21, 2016.

  1. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,124
    Likes:
    3,767
    Bristol
    I'm waiting for my 23andme results. I'm getting them done mainly to contribute to Nancy Klimas' call for genetic data crowdsourcing. It would obviously make sense to get some personal benefit too.

    There's lots of info splattered around the forum about genetic testing but if you find reading difficult ME wise it is hard to sort through. I'm hoping that people could summarise some info here? Perhaps you could then point people to this thread when we keep asking the same questions!

    My questions to people in the know such as @Valentijn @alicec @caledonia @Subcosmos @Flo @Sherpa @sregan are:

    With 23andme data

    1) which additional reports would you get done? Why?
    2) which give you the best control over seeing info useful for now and avoiding scary future stuff?
    3) what is worth checking if you have ME?
    4) what is worth looking for comorbidity wise eg Ehlers-danlos?
    5) what do people panic unnecessarily about?
    6) which report is on the money supplements advice wise?

    I want to get as much info as possible without ending up spending years worrying about potential diseases. On 23andme I won't open the Parkinsonism or Alzheimers info, but in other areas I think I want more information than they provide.

    I've seen Gene Genie recommended here is that http://geneticgenie.org?

    Promethease has also been recommended but when I ran their example test the 1st result was increased Parkinsonism risk which is precisely what I don't want to know. Someone else's screen printing seemed to show you can pick good and bad news. Initially I thought I could just pick good news but then realised you can probably infer the bad news by what's missing!

    I've also seen people recommend http://www.omim.org to interpret the meaning of results

    I want to make some decisions and get informed beforehand to avoid heartsinking moments over results that don't mean much. I'm doing this MOOC course on genetics and personalised medicine to get a better understanding https://www.coursera.org/learn/personalizedmed/home/info

    Thanks for your help.
     
    Last edited: Apr 22, 2016
    sarah darwins and Valentijn like this.
  2. Valentijn

    Valentijn WE ARE KINA

    Messages:
    14,281
    Likes:
    45,789
    It depends on what you're looking for. But keep in mind that 23andMe is only giving you a very small sample of your genome, so it could very well miss many things. But Promethease has a generally good reputation, with few errors.

    I also have a program at https://sourceforge.net/projects/analyzemygenes/ which can pull out your rare results (<=1% and <=10%). We have an extra download at https://sourceforge.net/projects/analyzemygenes/files/Databases/ called "remarks.zip" which is useful for sorting the ten_percent.zip results due to labeling genes and known pathogenic mutations, as well as a basic manner calculating scores regarding the likelihood of a missense or nonsense mutation being pathogenic.
    Genetically speaking, there aren't really any specific genes which are worth checking. Thus far, most of the SNP research involving ME has been junk (bad CFS definition, inappropriate or no controls, failure to correct for multiple comparisons, etc), and the results I have from 50+ ME patients on this forum generally contradict whatever is claimed in such research.
    The biggest problem seems to be a failure to understand the distinction between pathogenic (disease-causing) SNPs, rare SNPs, and SNPs associated with a small increase in risk of some disease. Pathogenic SNPs are the only ones to worry about, in my opinion, and even then the pathogenic ones will often be completely harmless if heterozygous, or only cause specific problems in specific circumstances such as not eating vegetables or taking a multivitamin during pregnancy with the common MTHFR mutations.

    SNPs associated with small risk increase of a disease are often complete bullshit. This problem isn't limited to CFS SNP research - there are a ton of studies out there with poor methodology. In fact, nearly all of them. I would not trust such research unless there is good methodology and it has been independently replicated. But most have not been replicated, so probably aren't reliable yet.

    And when those risk-associated SNPs are researched with good methodology and replicated, the effect size is always very small. It might look impressive that there's a x3 increase in risk in parkinson's, but if the risk is 0.1% to start with, it's only rising to 0.3% as a result of that theoretical SNP. That's not going to cause me any more concern than knowing about the 0.1% risk in the first place.

    The other problem I've seen is that people will extrapolate far beyond what is known about SNPs, and make assumptions that they are pathogenic simply because they are on a certain gene, or are somewhat rare. But the large majority of SNPs have no effect, and it is irrational to assume that unresearched SNPs have an effect, even if very rare.
    I haven't see any paid reports which are particularly accurate or helpful. I am especially unimpressed with nutrahacker, since they plagiarized my comments from this forum word for word regarding a CBS and an MTRR variant. In the process of looking more closely at their reports, it was apparent that they had no comprehension of genetics or methylation, and were probably looking to make some easy money by exploiting people with health concerns.

    Those are the types of things to ignore. If there actually is an association (you have to read the research closely to find out), it's a miniscule increase in risk. If it doesn't involve a missense mutation, nonsense mutation, or a splice-site or similar problem, it's going to be 99.9% irrelevant.

    OMIM is awesome. It collates all of the genetic SNPs which actually cause disease (or fundamental changes in how the gene functions), and doesn't include junk science or weak associations. The research is all cited there, and there's great information on the genes and diseases being discussed. The tricky part is that there are separate entries for genes and diseases, which some info on one of those but not the other. So it's often necessary to look up both the gene and the disease to see the full picture, but they're usually linked to each other at the top of each page.

    The other good one is dbSNP at http://www.ncbi.nlm.nih.gov/SNP/ . It flags missense mutations, shows prevalence rates of alleles and genotypes in general and specific populations, and links to research and usually OMIM if a variant of the SNP is pathogenic.

    SNPedia.com might be more user friendly for people who want very brief summaries of the research. But they tend to have some errors in prevalence rates, and the research summaries are often wrong. Though it can still be a good place to easily find research on specific topics, if willing to read the research itself instead of relying on the summaries.

    That's an excellent approach to take, for everyone who has the time and cognitive function. I took a few such courses on Coursera, and it really does answer a lot of your questions in the process ... and even more important questions I never thought to ask. It's pretty essential for everyone who really wants to understand the basics of genetics and their results, instead of blindly trusting interpretation systems which are often wrong (eg Yasko or blaming all rare SNPs).
     
    Last edited: Apr 21, 2016
    panckage, voner, rebar and 2 others like this.
  3. deleder2k

    deleder2k Senior Member

    Messages:
    1,104
    Likes:
    4,742
    Snowdrop and barbc56 like this.
  4. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,124
    Likes:
    3,767
    Bristol
    Thanks @Valentijn that will save me a lot of time trawling around the internet and perhaps some anxiety.
    The advantage of the Coursera courses is they're almost entirely video. My thinking is a lot better than my reading (as if the text on the page is curving, an ME acquired dyslexia thing).

    @deleder2k the impression I have so far is you don't get much info in the report from 23andme but the raw data can be useful if put through other sites (also I'm in the UK I think we get more info, not under FDA). Nancy Klimas thinks she can get useful stuff out of 23andme data research wise (although what's meaningful on a large scale maybe quite different from interpreting individual results).
     
    Valentijn likes this.
  5. caledonia

    caledonia

    Messages:
    4,203
    Likes:
    3,220
    Cincinnati, OH, USA
    I've found Genetic Genie (both methylation and detox reports) the most useful. If you can afford it, please do give a donation for that site. It was programmed by a member here who has ME and relies on donations to stay up.

    The other one to consider is Sterling's App from MTHFRsupport. It overlaps Genetic Genie but also goes much further into general health stuff. I've found it useful for a few selected SNPs, such as gluten, or anxiety. They are working on publishing explanations for everything and have the SNPs Compendium part 1 book completed so far. That was my main issue with that report was it was hard to interpret, but that is getting cleared up now.

    If you want to use the SNPs Interpretation Guide (see my signature link), it's based on Genetic Genie and much easier to use if you get that report (especially if have ME brain fog).

    As far as supplements, it's best to not treat yourself based solely on having certain SNPs. The reason is the SNPs are just potentials and may or may not be expressed. The SNP information needs to be coupled with functional testing such as the Nutreval test to see what is actually going on in your body.

    The other benefit of knowing your SNPs is understanding how and why your body works. Why you don't tolerate certain medications, which chemicals to avoid, why you get anxiety, and so on.
     
    Jenny TipsforME likes this.
  6. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,124
    Likes:
    3,767
    Bristol
    Thanks @caledonia.

    If other people want to use your interpretation guide (1) get 23andme data (2) put through http://geneticgenie.org (3) have a look at http://forums.phoenixrising.me/index.php?threads/snps-interpretation-guide.32187/

    https://www.gdx.net/uk/product/35 seems to be the UK link for Nutreval. What sort of price is it? It looks like you need a practitioner. Do all useful functional nutrition tests require a blood test, so therefore travelling to the practitioner? I'm not very able to get places. Are spit/urine/hair ones a waste of money? I've had adrenal ones done before by saliva: low DHEA, great morning cortisol then too low (speculation on my part due to my POTS when standing, as morning test before standing). I know from psychology experiments that saliva is an appropriate way to measure cortisol, but assume many nutrients only seen in blood.

    https://mthfrsupport.com/sterlings-app/ is link for the extra info you mentioned (assuming other people will use info on this thread). I've had celiac blood test before on NHS and was OK. Just about the only thing GP suggested rather than me! This will be a different measure SNPs wise? I'm one of those people definitely not celiac but perceive benefit from cutting out gluten when worse. My sister (also ME) like me lactose intolerant so will be surprised if that doesn't show up.
     
  7. Sea

    Sea Senior Member

    Messages:
    1,260
    Likes:
    2,618
    NSW Australia
    There is a wealth of information to be found from the 23andme test, but it doesn't necessarily come from the 23andme reports and it almost certainly won't be found in the information that is based on Yasko's theories. Complete genome testing would be better but 23andme is a good start.
     
    Valentijn and Jenny TipsforME like this.
  8. caledonia

    caledonia

    Messages:
    4,203
    Likes:
    3,220
    Cincinnati, OH, USA
    I'm not exactly sure about Europe, but the US price is around $800 (without insurance). I ordered mine from IntegrativePsychiatry.net, who has a physician on staff to sign off on it. That was all done online. Then I got the blood drawn at an independent lab in my area called Any Lab Test Now. Hopefully there is something similar in your area.

    Adrenal saliva tests are good. The Nutreval is blood and urine. It does require fasting. If you can't get the Nutreval, an OAT test (organic acids) covers some of the same territory and you might be able to use the Nutreval Interpretation Guide to partially interpret it.

    There is celiac (the worse one) and gluten intolerance. If you have gluten intolerance, it won't show up in a celiac test, but avoiding gluten is helpful. The only way to tell is to stop eating gluten and see if it helps. You can challenge test by reintroducing gluten after a time and see if you get worse.

    For toxic metals (mercury, lead, etc.) a hair test is actually the best. You need to order toxic elements + essential elements i. e. metals + minerals. Then interpret it with Andrew Cutler's counting rules to see if you have disordered mineral status. The metals may or may not show up directly. See my signature link for more info on Cutler, mercury chelation and the right hair test to get.
     
    Jenny TipsforME likes this.
  9. alicec

    alicec Senior Member

    Messages:
    1,375
    Likes:
    2,685
    Australia
    @Valentijn has covered it well.

    I would just like to emphasise that a proper perspective is necessary to benefit from a 23andme analysis and subsequent reports from others.

    Just because a variant is identified doesn't mean anything in itself. Unfortunately many of these reports imply the opposite or make little distinction between variants.

    Promethease is very extensive, ranks SNPs based on research and is searchable for any gene you are interested in. But you can't just accept what they say - you still need to look at the research and make your own decisions based on the various resources identified by @Valentijin.

    MTHFRsupport is also quite extensive and has helpful diagrams showing where all the various proteins fit into metabolic pathways. It also gives some links to research. However it does seem to be lacking quality control on reported variants. There are plenty of meaningless variants identified.

    Genetic Genie is much more limited. It reports just some detox SNPs and some methylation and methylation-related SNPs. It is based on SNPs that Yasko is interested in and perpetuates her mistakes and myths.

    Here is a post that discusses some of the relevant issues in evaluating SNPs.

    While it is possible that some rare SNP or SNPs of considerable consequence will be identified, it is more likely that a collection with small effect will be found. Identifying them is not going to be the answer to your health problems.

    The value as I see it is in identifying possible areas of weakness. These may not matter much if one is healthy and eating well. But we are not healthy and the more strain that is put on the system, the more likely that weaknesses will manifest themselves.

    There may be things we can do to support the weaknesses so they don't add to our problems - eg supplementing co-factors of sluggish enzymes may stimulate them a bit, or it may be necessary to supplement end products or intermediates further downstream to bypass the enzymes.

    I haven't seen any reports with reliable advice on work-arounds for SNPs. It is probably an individual thing anyway, evaluating your own areas of weakness.

    Adding an organic acid test can be very helpful in giving an overall picture about metabolic pathways which are not functioning well. Putting this together with your SNPs could be helpful in deciding on what action to take, but there is no direct link.

    The reason is not that SNPs are or are not expressed. If the gene is expressed, then the SNP will be. It is simply the case that each variant protein is only a tiny part of a very complex whole and the effect it exerts depends on many other factors which vary from individual to individual.

    .
     
    Jenny TipsforME and Valentijn like this.
  10. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,124
    Likes:
    3,767
    Bristol
    Right I've got my 23andme report. Nothing alarming (but didn't open Alzheimer's/Parkinson's/breast cancer).

    In fact makes me feel like there's an alternative me, out there in the multiverse, who is a slim sprinter effortlessly drinking lots of milky coffee ;) (I'm actually a bit overweight, obviously not doing any running, appear to react to milk though not genetic lactose intolerance and I'm not meant to drink caffeine on doctors orders)

    Main surprise is the lactose non-intolerance genetically. This is good news as problem probably gut or something and therefore ameniable to hacking. My sister very 'lactose intolerant' (also ME) so really expected that one to be genetic.

    I'm going to do the extra bits now.
     
  11. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,124
    Likes:
    3,767
    Bristol
    If other people want to use @Valentijn programme you need these instructions:

     
  12. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,124
    Likes:
    3,767
    Bristol
    @Valentijn used the programme - thanks!
    I've got 89 rare results but only one homozygous (which is
    rs9543107 13 T 0.01 TT)
     
    Valentijn likes this.
  13. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,124
    Likes:
    3,767
    Bristol
    @Valentijn @alicec @caledonia
    Can't find if anyone knows what that rs9543107 result means from online search. Possibly it's too rare to know at the moment? Something came up on OMIM as MTHFR but I think I searched wrong (though also know problems in that area are a likely candidate).
    I'll try genetic genie and come back to the rare ones.

    I assume a high number of rare results is actually the norm (in terms of there being loads of results so some are bound to be unusual). What numbers are other people getting?

    The rare results are fairly evenly spread out between different chromosomes eg 4-6 each.
     
  14. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,124
    Likes:
    3,767
    Bristol
    Yeah I do have some MTHFR issues (mentally insert some expletive vowels in my head to remember the consonants!). Including A1298C to do with neurotransmitters - gene 30% compromised for me. Is this something worth discussing with doctors or will they not know what to do with the information?

    I've got more homozygous to read up on.

    More than one thing related to BH4 which isn't something I've come across in my ME-patient-online-lay-doctor research.
     
  15. Valentijn

    Valentijn WE ARE KINA

    Messages:
    14,281
    Likes:
    45,789
    There's no research into it, and not much is known about the gene. The gene which that SNP is on activates AURKA, which is involved in centrosomes during mitosis.

    The program can generate up to 150 results from the earlier V3 chip, which tested more SNPs. Often the rare SNPs are not meaningful, and not located in the exons (coding sections) of genes. But the one you listed is a missense mutation, and rates a -2 on the BLOSUM62 scale due to the new amino acid being very different from the normal one, so it is capable of having a significant impact. But there's no way to really know for sure at this point whether it does or not, due to the lack of research.
     
    Jenny TipsforME likes this.
  16. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,124
    Likes:
    3,767
    Bristol
    @Valentijn that's annoying as it sounds like it might be useful for me to know. I'll check every so often

    It's going to take a while to understand it all. The temptation is to try to read everything today, but my brain won't cope with that.

    So far there's some face validity so I think it was worth doing. A few things to do with neurotransmitters, possible Mast cell issue, vitamins B12, D3 (though don't understand VDR relationship with COMT yet).

    My detox profile is looking more positive - no homozygous mutations, but a few hetero including 3 on CYP1B1, 2 on CYP2D6 (that's one I've heard of before on Coursera). Need to look up interpretation.
     
  17. Jenny TipsforME

    Jenny TipsforME Senior Member

    Messages:
    1,124
    Likes:
    3,767
    Bristol
    @caledonia I'm reading your helpful 2014 SNP interpretation guide but most of the early on links seem to have moved (except video and Yasko).

    Unfortunately if I'm reading right I've got “BH4 deficiency double whammy” including 2 homo mutations in BHMT and hetero in both CBS as well as hetero in MTHFR A1298C. Also MAO A and MTRR homozy issue probably doesn't help (don't identify as mood swings though). This doesn't seem like a very pretty picture, even if only some of it expressed, although very helpful to know the relationship and ideas on how to sort it out supplement wise. This seems like it should be a priority focus.
     
  18. Valentijn

    Valentijn WE ARE KINA

    Messages:
    14,281
    Likes:
    45,789
    These should be having very little impact, if any at all.
     
    Jenny TipsforME likes this.
  19. PennyIA

    PennyIA Senior Member

    Messages:
    718
    Likes:
    1,663
    Iowa
    I would agree that, the test reports are bunk... but the raw data has been very useful for me and far less expensive than testing through my doctor's office ($299 for testing 2 SNPs at the doctors office with him misstating the results vs. $99 for 23andme)... I've totally ignored the test reports... but regularly and routinely look at specific SNPs as I learn about them here and then try to dig out specific research reports on the same SNPs to see if it validates (or contradicts or seems to have been verified via other testing).

    For example, my eldest son & I both have homozygous a1298c; and there's been five separate (albeit small) studies that indicate it can be linked to male infertility - repeated in different countries on different sized groups, but a1298c males tend to have severe fertility issues about 90% of the time.. Since he'd been trying to get his wife pregnant for over a year - I suggested he try methylfolate and methylcobalamin- albeit, there wasn't any testing of any sort supporting that methylation support improves outcomes... but knowing he had MTHFR defects and that he seemed to be struggling with fertility, I didn't think small doses would hurt and might help with some other issues. He made me a grandma within about 10 months of starting treatment. Without 23andme I wouldn't have had the basis of information that might have helped (not that I'm sure it did help, it might have been completely unrelated timing... but hey, it helped me with my research and I could at least feel like I was helping).
     
    Jenny TipsforME and Valentijn like this.
  20. caledonia

    caledonia

    Messages:
    4,203
    Likes:
    3,220
    Cincinnati, OH, USA
    Sounds like you're set up for mental health issues. COMT is more associated with mood swings.

    Thanks for the heads up on the links. You can try putting them into the Internet Archive Wayback Machine and see if archived versions come up there. https://archive.org/web/
     

See more popular forum discussions.

Share This Page