The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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Reading snps C/T or A/G???

Discussion in 'Genetic Testing and SNPs' started by sregan, Nov 10, 2016.

  1. sregan

    sregan Senior Member

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    rs3892097

    23 and me gives:

    CYP2D6 rs3892097 42524947 C or T, C / C

    Description of the gene is giving A and G....

    Found this article seems to be saying A == T and C == G? Is that correct?
     
  2. alicec

    alicec Senior Member

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    DNA consists of two strands bonded together through the nucleobases C G A T the order of which specifies the coding information. C is always paired with G, A with T.

    So if you know the coding sequence of one strand, you know that the other strand will be the alternative - ie CGAT on one, GCTA on the opposite.

    So the two sources you quote are just reporting results for opposite strands.

    When a SNP involves a change from C to T as in your example - ie bases which don't pair with each other - it doesn't matter which strand the result is reported from. You can always work out if you have the variant or wild-type allele.

    When a SNP involves a change from G to C or from A to T you need to know which strand the result is coming from to know which version you have.

    23andme always reports results for the forward or plus strand, but other sources might report from either strand (the opposite strand is usually designated - or reverse).

    You can always check this here by just typing in the rs number of the SNP you are interested in. You will get a lot of information, including which allele is wild type, which is variant (including the orientation) as well as frequency in the population, references to research, etc.
     
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  3. sregan

    sregan Senior Member

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    I'm trying to determine based on genome which antidepressants might be effective or not. Especially which ones should be avoided. Is there a pay service? Prometheous maybe?

    Something this article is talking about.
     
    Last edited: Nov 11, 2016
  4. sregan

    sregan Senior Member

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    Or something that might use my 23andme genome and give me information like this Genesight
     
  5. alicec

    alicec Senior Member

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    The two approaches in your links are largely looking at different things. The first is trying to identify genetic association with the biological response to antidepressants - ie SNPs in pathways affecting neurotransmitters.

    The second is mainly looking at SNPs which affect metabolism - the rate at which drugs are broken down, though they do tack on a couple of SNPs relating to serotonin transport and uptake.

    You should be able to get some insight into drug metabolism by running your 23andme results through Promethease. They do a fair job of looking at detox SNPs and you can see from the info from Genesight which genes they are testing for.

    You can search Promethease for these genes.

    The Genesight test may give more information and may include SNPs which 23andme doesn't look at though you would need to look at an actual test to really determine that. It would certainly be a quick way of getting targeted information, BUT I imagine there would be a fairly substantial charge for this test.

    As for the first approach, there is nothing to stop you noting the rs numbers of the SNPs which they identify as being associated with anti-depressant response and searching for them in your raw 23andme results. They may or may not be analysed.

    Assuming they are, you would then need to read the research to determine which alleles are associated with the effect and whether these are the ones that you have.

    Note, however, that they are talking about small effects so it's hard to say whether there would be much benefit flowing from what could be a long research effort on your part, given that you seem to be a beginner.

    I doubt that you will find any of the 23andme analysis programs which would include relatively recent research like this on so specific a topic but I guess you won't know until you look.
     
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  6. sregan

    sregan Senior Member

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    @allcec, I ran Promethease last night and it pulls data from snpedia.com to fill the report. I'm wondering, as you mentioned, if Genesight has more information on certain genes than is generally available to the public? They're service seems to be geared toward appropriate dosage based on liver clearance speed (the 6 CPY genes) and then toward response of the actual medication itself (SLC6A4 and HTR2A).

    What Genesight looks at according to their website


    It seemed like there could be a lot more genes to look at to determine drug response than just what's in those two? But I'm definitely no expert here.
     
  7. sregan

    sregan Senior Member

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    This free service also pulls from snpedia.com and does a pretty good job. Promethease looks like it might have some better filtering and organizing but this one looks really good.

    It's got a nice searching ability at the top. I would say try this one first.

    Side by side is showing some differences:

    https://codegen.eu
    rs4148739(A;A) info:1.62 73.04%7x less likely to respond to certain antidepressants

    Promethease:
    rs4148739(A;A) 71.7% Frequency 7x less likely to respond to certain antidepressants


    https://www.nutrahacker.com/ has got a Depression and Depression Side effect report that look very close to what I was asking about
     
    Last edited: Nov 12, 2016
  8. alicec

    alicec Senior Member

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    The only way to know that is to see a report and determine if they test for SNPs which 23andme doesn't look at. You also get their interpretation which one presumes is informed by experts in pharmacogenomics, rather than relying on your own resources.

    The CYP genes tested are the important ones for drug metabolism. As for the biological response, well the review you linked suggests a number with small effect but the analysis programs might not have caught up with all the research yet, or it might not be sufficiently codified for them to include an estimate of effect.

    You would need to do more reading to try to find out why genesight settled on the two that it did.

    There seem to be a number of new analysis sites appearing. For the most part they now seem to realise that just identifying the presence of variants is a waste of time - we need to know if the variants have any effect. Hence they usually rank SNPs based on research.

    If they are free or cost very little then look at as many as you can find and compare info. Be sceptical however about added recommendations (supplements etc) such as those of Nutrahacker. These are often very dubious.

    The difference you noted between Promethease and Codegen doesn't seem very significant. The slight difference in frequency reported might just reflect the time that they got the information from a database. These are being updated all the time and frequency will change slightly as more genomes are added. The dsSNP link I gave you previously is the best place to look for up to date database info.
     
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