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Let's Explore Other SNP's (APOE Status, Liver pathways etc) Feel free to add!

Discussion in 'Genetic Testing and SNPs' started by Calico13, Apr 17, 2012.

  1. Calico13

    Calico13

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    Hey everyone! All of you who have tested through 23andme or any other genotyping or genome sequencing company, will be able to participate in this thread. :) I'm still learning this stuff, so bear with me.

    I feel we need to take a deeper look into our raw data and start collecting SNP's that may be of interest to CFS, POTS and any other chronic illnesses we all suffer from. I hope to continue adding to this list. I will try to keep this post edited with all of the important SNP's mentioned. If you could please keep the Dr Amy Yasko methylation SNP's out of this thread, I'd appreciate it. There are many threads on this topic and I wanted to explore new areas. :thumbsup:

    *Get SNPtips for Firefox
    If you have not done so yet, I highly recommend installing a Firefox addon called SNPtips that will make checking your genotypes a lot easier while browsing the web. With this addon installed, all RS Id's will become clickable and will allow you to see your genotype without having to even visit the 23andme website. This thread will be written as if you have SNPtips installed. I'm not going to be directly linking back to 23andme when there's an addon that does it for you. Sorry. Even if you don't use firefox usually, I recommend downloading it and using it while looking at genetic information.

    *Recommended 3rd Party Tools
    There is a website that lists a bunch of 3rd party tools you can use to get more information out of your data. You can find that here.
    http://www.23andyou.com/3rdparty

    Promethease-Highly recommended http://snpedia.com/index.php/Promethease This program will run your raw data through their system and flag specific SNP's that have been studied to increase your risk for diseases or seen more often in certain conditions etc. It is going to find things that 23andme does not report on. I found out some amazing stuff with this tool. If you have run your data through Promethease and found something interesting, please post the related RS Id's with a brief description, so we can all take a look. I will keep this post edited (as often as I can) with all of the SNP's mentioned.

    Interpretome-Very similar to Promethease. http://esquilax.stanford.edu/ It will give you data based upon your genotypes on specific SNPs.

    ROH and No Call Strings Check-http://www.math.mun.ca/~dapike/23roh.php This utiltity will look at your raw data and see how much homozygosity is in your genetics. Typically one would call this "how inbred" you are... It will also check for No Call strings which may indicate a mutation or microdeletion. I can't offer detailed support with this tool as I am learning it on my own, but I can give general ideas of what the data means. Please see this 23andme thread for more information. https://www.23andme.com/you/community/thread/3093/

    ___________________________________________________________________________________________________________________

    * APOE Status
    APOE E4 is considered the bad one. It has been implicated in alzheimer's. Those with the genetic allele ApoE4 protein in the blood have been found to detoxify metals poorly and to be much more genetically susceptible to chronic neurological conditions than those with types ApoE2 or E3 Source

    23andme files this under the Alzheimer's health report. This one is determined by 2 SNP's and it can be a little confusing, so I recommend taking a look at the report.
    https://www.23andme.com/you/journal/alzheimers/overview/

    If you have data from another company, then these are the 2 Rs Id's associated with it. It is more difficult to determine than a simple TT or CC.
    [table="width: 250, class: grid, align: left"]
    [tr]
    [td]APOE [/td]
    [td]Rs429358[/td]
    [td]Rs7412[/td]
    [/tr]
    [tr]
    [td]e2[/td]
    [td]T[/td]
    [td]T[/td]
    [/tr]
    [tr]
    [td]e3[/td]
    [td]T[/td]
    [td]C[/td]
    [/tr]
    [tr]
    [td]e4[/td]
    [td]C[/td]
    [td]C[/td]
    [/tr]
    [/table]

    If you are CT at rs429358 and CC at rs7412 you would be e3/e4.
    If you are TT at rs429358 and CC at rs7412 you would be e3/e3. This is most common.
    If you are CC or CT at rs429358 and CT at rs7412 you would be e2/e4 or the rare e3r. This combo is rare and not well understood. See this study.
    If you are CC at rs429358 and CC at rs7412 you would be e4/e4.
    If you are TT at rs429358 and CT at rs7412 you would be e2/e3.

    This should cover all possible variations. CC at rs429358 and TT at rs7412 has never been seen according to 23andme.

    *Liver Pathways
    With liver pathways, there are a ton of SNP's, so only a few of them are listed here.

    CYP1A2 is one of the main liver pathways which metabolizes caffeine, estrogen, naproxen, propranolol, acetaminophen and many many more drugs. Here's a link to more data about this from mayo clinic.

    CYP1A2 rs762551 Each C is a copy of slower function.
    Therefore AA=normal; AC=intermediate ; CC=slow metabolism
    23andme has a report on this here. https://www.23andme.com/you/journal/pre_caffeine_metabolism/overview/

    More SNPs related to CYP1A2 are listed here at SNPedia. http://www.snpedia.com/index.php/CYP1A2
    _______________________________________________________________________________________________________________

    CYP2C9 is another liver pathway which metabolizes Warfarin, NSAID's, aspirin, phenytoin and more. Here's a link to data from Mayo Clinic.

    CYP2C9*2 rs1799853 Each T is a copy of slower function.
    Therefore CC=normal; CT=intermediate TT=Slow
    CYP2C9*3 rs1057910 Each C is a copy of slower function.
    Therefore TT=Normal; CT=Intermediate CC=Slow

    More SNP's related to CYP2C9 are listed here at SNPedia. http://www.snpedia.com/index.php/CYP2C9
    _____________________________________________________________________________________________________________

    CYP2D6(Directly from SNPedia) Almost 25% of all drugs are metabolized by CYP2D6, including dextromethorphan (a key ingredient in products such as Nyquil), beta-blockers, antiarrhythmics, and antidepressants.

    This one is not easily decided by a single SNP, so I looked at the genoset 182 at SNPedia to determine this. I'm not entirely sure how this one is determine. I highly recommend seeing what Promethease has to say about your result specifically.
    rs1135840 G=risk allele for rapid metabolism
    rs16947 A=risk allele for rapid metabolism

    A word of caution from SNPedia, "Please be careful when interpreting results for this SNP as it is in dbSNP and SNPedia in minus orientation where the risk allele is C, but test results are usually in plus orientation where the risk allele is G. This SNP has an ambiguous flip which can make this very confusing. "
    _____________________________________________________________________________________________________________

    NAT2 (Directly from SNPedia) N-acetyltransferases are enzymes acting primarily in the liver to detoxify a large number of chemicals, including caffeine and several prescribed drugs. The NAT2 acetylation polymorphism is important because of its primary role in the activation and/or deactivation of many chemicals in the body's environment, including those produced by cigarettes as well as aromatic amine and hydrazine drugs used medicinally.

    Interpreting the alleles for this is more confusing. Check out this website and input your genotypes to find out whether you are rapid, intermediate or slow.

    These are the SNP's and corresponding positions, so you know what to input.
    NAT2 sequence position with RS ID's
    282 =Rs1041983
    341= Rs1801280
    481= Rs1799929
    590= Rs1799930
    803= Rs1208
    857= Rs1799931


    Preliminary data suggests Rs1495741 accurately predicts NAT2 metabolism. Each copy of A suggests slow metabolism.
    Therefore GG=Rapid; AG=Intermediate; AA=Slow

    In this thread, LaurieL posted a study that found rapid NAT2 and CYP2D6 metabolism was seen more often in those with Multiple chemical sensitivity than in controls.

    For more information on this pathway see SNPedia http://www.snpedia.com/index.php/NAT2 and Promethease.
    __________________________________________________________________________________________________________________________________
    VKORC1 is related to Warfarin metabolism and vitamin K recycling.

    Rs9923231 For each T=increased sensitivity to Warfarin. This genotype frequency is highly varied among different populations.
    For more information on drug metabolism and liver pathways see the article on SNPedia. There are many more I did not list here.
    ________________________________________________________________________________________________________

    *Celiac Disease
    Rs2187668= For each T, increases risk. This is testing for HLA-DRB1*0301 or the DQ2.5 Haplotype. This SNP is also associated with other autoimmune disorders.
    rs6822844= For each G, increases risk.
    rs6441961= For each T, increases risk.
    Rs2074404=GG Seen in higher rate in those with Celiac
    _________________________________________________________________________________________________________________

    Sections I'd like to add in the future after more research:
    Autoimmune SNP's for lupus, sjorgren's etc.
    Collagen SNP's for connective tissues disorders and EDS
    HLA data if this can be figured out... Many people online are still trying to do this. It is not available yet.
    Give me some ideas/suggestions...
    Radio, NilaJones, Sea and 1 other person like this.
  2. Calico13

    Calico13

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    *Reserved* Just in case I run out of room!
  3. Calico13

    Calico13

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    My results

    I am APOE E3/E3
    rs429358 TT
    rs7412 CC

    CYP1A2 rs762551 CC=Slow metabolism
    CYP2C9*2 rs1799853 CC=Normal metabolism
    CYP2C9*3 rs1057910 AC=Intermediate metabolism
    CYP2D6 rs1135840 CC=Normal Metabolism
    CYP2D6 rs16947 GG=Normal Metabolism
    NAT2 Rs1495741 AA=Slow metabolism
    VKORC1 Rs9923231 CT=Intermediate metabolism

    Celiac Disease
    Rs2187668 CC= Lower risk. I don't have DQ2.5 haplotype.
    rs6822844 GG= Higher risk
    rs6441961 CC= Normal risk
    Rs2074404 GG=Higher risk
  4. roxie60

    roxie60 Senior Member

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    Central Illinois, USA
  5. roxie60

    roxie60 Senior Member

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    I am APOE E2/E4

    rs429358 CT
    rs7412 CT

    no wonder I'm always fighting myself :) Also I think a rare combination but dont know what it means. maybe that just didnt have enough E2/E4s in their study
  6. roxie60

    roxie60 Senior Member

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    I am trying to make sense of the NAT2 SNPs above. There is the predictor SNP Rs1495741 (I am AA - slow) but if I look at the 6 individual NAT2 SNPs listed above half are slow and half are fast (I think) so how do I end up considered slow - there must be something I am missing.

    NAT2 sequence position with RS ID's
    282 =Rs1041983 CC - rapid (in my doc I have this as slow)
    341= Rs1801280 CC - rapid (in my doc I have this as slow)
    481= Rs1799929 TT - slow
    590= Rs1799930 GG - rapid
    803= Rs1208 GG - rapid
    857= Rs1799931 GG - rapid

    Can someone help me understand where I am missing how I come up slow metabolizer with these alleles? Thx

    Also I have multiple chemical sensitivities but my rs1495741 indicates slow metabolizer, I have issues with CYP2D6 so if my interpretation of the 6 NAT2 of which most are rapid (not slow) and combined with CYP2D6 that lines up. But the rs1495741 as indicator of NAT2 slow metabolizer doesn't line up. I really want to understand this. Also can I presume there is no actual risk allele associated with these NAT2 SNPs just rapid normal and slow?
  7. Sea

    Sea Senior Member

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    Very interesting thread calico

    My results

    I am APOE E3/E4
    rs429358 CT
    rs7412 CC

    CYP1A2 rs762551 AA =
    CYP2C9*2 rs1799853 CC=Normal metabolism
    CYP2C9*3 rs1057910 AA =
    CYP2D6 rs1135840 AG =
    CYP2D6 rs16947 CG =
    NAT2 Rs1495741 AA=Slow metabolism
    VKORC1 Rs9923231 CT=Intermediate metabolism

    I've left the designations of slow etc where my results are the same as yours Calico, but where I'm different I don't know what to put. Where did you get that info from?

    NAT2 results
    282 =Rs1041983 CC
    341= Rs1801280 CC
    481= Rs1799929 TT
    590= Rs1799930 GG
    803= Rs1208 GG
    857= Rs1799931 GG

    Final prediction= Slow

    Celiac Disease
    Rs2187668 CC= Lower risk. I don't have DQ2.5 haplotype.
    rs6822844 GG= Higher risk
    rs6441961 CC= Normal risk
    Rs2074404 TT =

    From Promethease my results for Celiac were flagged as genoset 221 criteria: and(rs2395182(T), rs7775228(C), not(rs4713586(C)

    rs2395182 GT
    rs7775228 CT
    rs4713586 snp not tested by 23andme
  8. Thinktank

    Thinktank Senior Member

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    Bangkok, Thailand
    That's all for 23andme results right?

    How would that translate to my genova diagnostics detoxification results?
    I fail to understand how my phase 1 and 2 clearance are balanced. Is phase 1 too slow or too fast? How about phase 2?
    I can't wait for the 23and me and yasko's results to come in so i can dive deeper into this whole very interesting science of SNP's.
    I know how to help my body wit the the double mutation in SOD2 but the other things are still a mystery to me. Any input would be highly appreciated!

    My results:

    CYP 450 Polymorphisms:
    CYP2C9
    CYP2E1

    Acethylation (n-acetyltransferase)
    Slow metabolizer polymorphism
    +- NAT2 I114T
    +- NAT2 R197Q

    Acethylation (n-acetyltransferase)
    Fast metabolizer polymorphism
    +-NAT2 K268R

    Glutathione conjugation
    +- GSTP1 I105V
    +- GSTP1 A114V

    Oxidative protection
    ++ SOD2
  9. roxie60

    roxie60 Senior Member

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    I have a double mutation on SOD2 and would like to know where you found info on helping with that mutation, thx
  10. NilaJones

    NilaJones Senior Member

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    Awesome thread, Calico13!

    Did you ever look into collagen SNP's for connective tissues disorders and EDS?
    leela likes this.
  11. roxie60

    roxie60 Senior Member

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    So SOD2 protects one from oxidative stress ?

    Oxidative protection
    ++ SOD2
  12. Critterina

    Critterina Senior Member

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    Roxie, I struggled through this with my own NAT2, and ended up using a predictor where you put in your SNPs and it did the calculation for you. It's haplotype dependent. I cut and pasted the following from a website into my "mutation map":
    Alternatively, NAT2 acetylator phenotype can be inferred from a complex NAT2 genotype (i.e. a combination of SNPs observed in a given individual) using the publicly-accessible web-server NAT2PRED (http://nat2pred.rit.albany.edu). [PMID 19261719]
    roxie60 likes this.
  13. Critterina

    Critterina Senior Member

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    Has anyone figured out the risk alleles for HNMT? I'd love to know that.
  14. roxie60

    roxie60 Senior Member

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    I did use this tool which is what started my question, it shows me as SLOW metabolizer and yet the documentation I have indicates 84% of my snps are RAPID metabolizers, just trying to understand how this tool comes up with SLOW when most doc would indicate RAPID. Which results to trust?

    Final Prediction : SLOW (0.997183)
  15. roxie60

    roxie60 Senior Member

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    23andMe shows 49 snps, are you looking for the risk alleles for all of them?
  16. roxie60

    roxie60 Senior Member

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    rs1349992 appears to have risk allele 'A' per dbSNP http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs1349992 If I am reading it correctly this is the minor/risk allele. Someone correct me if not interpreting dbSNP correctly (I interpret all minor alleles as the risk alleles). I am AA on this HNMT snp.
  17. Critterina

    Critterina Senior Member

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    The thing that confused me was whether I was looking at the positive or negative strand for all this, and then, after figuring that out, it turns out that it's a haplotype-issue: individual SNPs don't make as much difference as what combinations you have. The same PMID article said:

    NAT2*4: considered to be the wild-type allele, and the exemplar rapid metabolizer;
    consists of the first nucleotide shown in the "aka" (also known as) names listed above for these seven NAT2 SNPs, i.e. an allele in question is NAT2*4 if it is rs1801279(G) and rs1041983(C) and rs1801280(T) and ... etc
    Almost all of the remaining common alleles are slow metabolizers, such as:

    NAT2*5A: 341C + 481T, i.e. rs1801280(C) + rs1799929(T)
    NAT2*5B: 341C + 481T + 803G, i.e. rs1801280(C) + rs1799929(T) + rs1208(G)
    NAT2*5C: 341C + 803G, i.e. rs1801280(C) + rs1208(G)
    NAT2*5D: 341C, i.e. rs1801280(C)
    NAT2*5E: 341C + 590A, i.e. rs1801280(C) + rs1799930(A)
    NAT2*5G: 282T + 341C + 481T + 803G, i.e. rs1041983(T) + rs1801280(C) + rs1799929(T) + rs1208(G)
    NAT2*5J: 282T + 341C + 590A, i.e. rs1041983(T) + rs1801280(C) + rs1799930(A)
    NAT2*6A: 282T + 590A, i.e. rs1041983(T) + rs1799930(A)
    NAT2*6B: 590A (only), i.e. no variation compared to NAT2*4 except rs1799930(A)
    NAT2*6C: 282T + 590A + 803G, i.e. rs1041983(T) + rs1799930(A) + rs1208(G)
    NAT2*6E: 481T + 590A, i.e. rs1799929(T) + rs1799930(A)
    NAT2*7A: 857A (only), i.e. rs1799931(A)
    NAT2*7B: 282T + 857A, i.e. rs1041983(T) + rs1799931(A)
    NAT2*14A: 191A, i.e. rs1801279(A)
    NAT2*14B: 191A + 282T, i.e. rs1801279(A) + rs1041983(T)
    NAT2*14C: 191A + 341C + 481T + 803G, i.e. rs1801279(A) + rs1801280(C) + rs1799929(T) + rs1208(G)
    NAT2*14D: 191A + 282T + 590A, i.e. rs1801279(A) + rs1041983(T) + rs1799930(A)
    NAT2*14E: 191A + 803G, i.e. rs1801279(A) + rs1208(G)
    NAT2*14F: 191A + 341C + 803G, i.e. rs1801279(A) + rs1801280(C) + rs1208(G)
    NAT2*14G: 191A + 282T + 803G, i.e. rs1801279(A) + rs1041983(T) + rs1208(G)

    However there are also a few rapid (i.e. normal) metabolizer variants as well, such as:

    NAT2*11A: 481T, i.e. rs1799929(T)
    NAT2*12A: 803G, i.e. rs1208(G)
    NAT2*12B: 282T + 803G, i.e. rs1041983(T) + rs1208(G)
    NAT2*12C: 481T + 803G, i.e. rs1799929(T) + rs1208(G)
    NAT2*13: 282T (only), i.e. rs1041983(T)
  18. Critterina

    Critterina Senior Member

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    Yes, I'm trying to find all the risk alleles and then look at the research for each. One of my really limiting health problems is histamine intolerance. I get the DAO gene, and how that may contribute to my problem (although must of the research is in relation to schizophrenia and bipolar disorder). I want to understand if the HNMT could be contributing, too.
    The only way I know to do this is to go to the dbSNP and just scroll along the whole gene, finding the clinically pathological associations and reading the research. Some of the other identified variants are interesting, too. I'm not sure why they are not considered pathological, because sometimes they are associated with bad things. I just haven't had time.
  19. Sea

    Sea Senior Member

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    NSW Australia
    Thinktank roxie60

    I don't know if you followed the previous discussion all the way through about the SODA16V mutation. It seems that there is some disagreement about which way the change has gone A-V or V-A, but the G allele corresponds to Alanine (A) and the risks are all with Valine (V)

    SOD2 A16V homozygous mutation - anyone else?
    roxie60 likes this.
  20. roxie60

    roxie60 Senior Member

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    Critterina Ok I think I get it. That tool is based on those 8 snps (per PMID) and depending on the status of each one, combined they are predictors of SLOW or RAPID metabolizers. So it looks like if you have two of the four snps then all the others are considered slow metabolizers (except the ones u listed as FAST/RAPID). There was one statement in that PMID that seemed to imply more study needed to verify the halotype overides the individual snps. So I wonder if you can be SLOW as this study indicates but still have some RAPID snps still affect metabolism. I think this is important to understand since many of us have issues with reactions to various medications and supplements.

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