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Genetic SNPs Poll

Discussion in 'Genetic Testing and SNPs' started by Soundthealarm21, Jan 5, 2014.

?

What Genetic SNPs have you tested positive for?

  1. COMT V158M

    64.3%
  2. COMT H62H

    64.3%
  3. COMT P199P

    10.7%
  4. VDR Bsm

    67.9%
  5. VDR Taq

    82.1%
  6. MAO A R297R

    78.6%
  7. ACAT1- 02

    10.7%
  8. MTHFR C677T

    57.1%
  9. MTHFR 03 P39P

    21.4%
  10. MTHFR A1298C

    46.4%
  11. MTR A2756G

    25.0%
  12. MTRR

    85.7%
  13. BHMT 1, 02, 04, 08

    75.0%
  14. AHCY 01, 02, 19

    17.9%
  15. CBS C699T

    60.7%
  16. CBS A360A

    39.3%
  17. CBS N212N

    0 vote(s)
    0.0%
  18. SHMT1 C1420T

    39.3%
  19. NOS D298E

    7.1%
  20. I do not have a SNP on the methylation pathway

    0 vote(s)
    0.0%
Multiple votes are allowed.
  1. Soundthealarm21

    Soundthealarm21 Senior Member

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    Dallas, TX

    I thought only I could see that. I don't know why they're bold and asterisked, but those are the ones I voted for.
    MeSci likes this.
  2. SOC

    SOC Moderator and Senior Member

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    :wide-eyed: It sure is! :wide-eyed: I have trouble even reading my data, much less copying it snp by snp. :p

    While I'm disappointed not to be included in the magnificent Gigantor Excel Spreadsheet of Genetic Doom, I understand that it is currently impossible.

    Thanks for your impressive work collating and correlating our genetic data.
  3. taniaaust1

    taniaaust1 Senior Member

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    Thanks greatly for that :) .. someone had told me it was one of the rarer mutations.. seems they must of given me the wrong info.

    I can see from Valenijn's graphs that fairly equal between the two groups with the ME group only having one extra double copy person of it (thanks a lot Valenijn, its good when I cross out one thought). I still wonder thou if its causing lithium issues in people with double copies of it... even maybe some healthy people may have lithium deficiency.
  4. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    But women seem more likely to get ME (with the same gene mixes as men who don't?) so might that confound things? It might be best to do separate charts for men and women, especially as Valentijn clearly doesn't have enough to do...;)
    Valentijn likes this.
  5. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Do we know if lithium plays a significant role in human biochemistry?

    I found this page which says we don't really know.
  6. taniaaust1

    taniaaust1 Senior Member

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    I cant remember now what I read about it but I do know that research has shown that taking lithium.. can raise white blood count. And that is exactly what it did with me when I took it for my deficiency, it double my count and now its in a good range.
    .......

    On that link you just gave it appears it also affects the immune system in other ways.. from the link see the part I bolded
    Last edited: Jan 7, 2014
  7. Valentijn

    Valentijn Activity Level: 3

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    Yeah, there's got to be a sex-related factor in there somewhere. But for purposes of purely genetic comparison, men should work just fine as controls . Also I'm quite fond of my first 6 listed controls, as they all definitely don't have ME/CFS or even pain or fatigue issues :D
    SOC and MeSci like this.
  8. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    ...don't forget to control for ethnicity too, when you get round to your PhD thesis! :D
    Soundthealarm21 and Valentijn like this.
  9. SOC

    SOC Moderator and Senior Member

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    Going by this poll, I'm really in with the In crowd. ;) I have all the mutations that more than 50% of us have except the CBS C699T. I have the CBS A360A mutation instead. I also don't have any of the less than 50% mutations except the CBS A360A.

    :whistle: "I'm in with the In crowd. I go where the In crowd goes. I'm in with the In crowd. I know what the In crowd knows." :whistle:

    I know, I'm dating myself. If I could figure out how to embed audio of this 70's favorite for the edification of the young'uns, I would.
    madietodd and Valentijn like this.
  10. SickOfSickness

    SickOfSickness Senior Member

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    Could you explain this further? In an old post of yours, I believe you said when analyzemygenes runs with the 1% database, it is finding mutations that less than 1 in 10000 people have. I may have interpreted your post wrong. Why doesn't this 1% figure mean 1 in 100 people?

    And I was looking at dbSNP and (if I am not interpreting it wrong) they said the frequency number they post is the middle number, not the lowest number. So is analyzemygenes also using the middle number and not lowest?

    And further can someone confirm that middle number means heterozygous mutation frequency? I'm trying to piece this together. If we are examining a specific SNP of a gene, and 1 in 4000 people have a heterozygous mutation and 1 in 10000 people have the homozygous mutation, then it is 1% for homozygous, but analyzemygenes will put 2.5%.

    Edited to add: I am further confused because of mutations which are only in a certain ethic group. Say 2% of that ethnic group has a mutation but 0% of caucasians and 0% of every other ethnic group. I believe the number reported by these sites will say 2% which doesn't take into account that the first ethnic group has a low population.
    Last edited: Jan 7, 2014
    Valentijn likes this.
  11. Valentijn

    Valentijn Activity Level: 3

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    The 1% file is looking at SNPs with a prevalence of 1% (0.01) or less. Homozygous results returned from that database would have a prevalence of 0.01 squared (0.01 x 0.01). That works out to 0.01% (0.0001), or 1 in 10,000.

    If allele prevalence is 10%, then the homozygous genotype prevalence is 0.1 x 0.1 = 0.01, or 1%. So "rare" mutations listed above have a much higher allele prevalence than the 1% in the rare gene analysis program - going up to 31.6% allele rate for homozygous mutations to be at 10% or less, and going up to 5.3% allele rate for heterozygous mutations to be at 10% or less.

    So this isn't looking at super duper rare mutations (that's what the rare genes analysis program does), but rather looking for relatively rare genotypes shared by ME/CFS patients when compared to controls. That way trends across a gene (or multiple genes with a similar function) can be spotted, instead of just identical very rare SNPs shared by multiple patients.
    Both dbSNP and the rare genes analysis program use 1000 Genomes as the data source for minor allele frequency. Hence they should be the same, unless dbSNP hasn't gotten the most recent update from 1000 Genomes.
    Analyzymygenes is indicating minor allele frequency (MAF). Genotype frequency can be calculated from the MAF:
    Homozygous = MAF x MAF
    Heterozygous = 2 x (1 - MAF) x MAF
    The frequencies given are across all populations. Ethnic rates are available, but much less relevant, in my opinion. Genes function as they function, regardless of ethnicity - there may be some variations due to interactions with other SNPs which are more or less common in that group, but it's still coming down to the genes. Is an SNP with 25% prevalence in general, but 5% prevalence in Caucasians going to be relevant to causing a fairly rare disease? Probably not, hence me not giving a damn if it's rare in a tiny and insular sample of people which isn't even properly representative of Europeans :D Using data from a specific ethnicity would also be arbitrarily exclusionary toward non-Europeans, and I far prefer an inclusive approach.
    SOC likes this.
  12. SickOfSickness

    SickOfSickness Senior Member

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    Prevalence was confusing. So analyzemygenes looks at the 1000 Genes database for MAF of .01 (or less) or .1 (or less) and ignores higher. So if someone runs the program with 1% and they are homozygous that means 1 in 10,000 people share it (or less). If they are heterozygous that is about 1 in 50? (2 * .99 * .01 = 0.0198)

    So if analyzemygenes says 2% that's 0.02 MAF. So 1 in 2500 people have the homozygous and around 1 in 25 have heterozygous? This does not seem possible to me but it may be because it's hard to imagine this for every SNP that contributes to one condition or disease.
  13. madietodd

    madietodd Senior Member

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    I looked for information about my homozygous MAO gene. If I understand the chart correctly, almost 70% of the European population has my TT variant. Is this right?

    http://snpedia.com/index.php/Rs6323

    [I can't figure out how to embed a link in this new software]
    Last edited: Jan 7, 2014
  14. SickOfSickness

    SickOfSickness Senior Member

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    Have you seen the bar graphs on this page near the bottom? May be easier to understand. http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=6323
  15. Valentijn

    Valentijn Activity Level: 3

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    Yup, those calculations all look correct. Heterozygous mutations are MUCH more common than minor allele homozygous homozygous, especially as the rare allele gets rarer. A way to check your calculations is to figure out the frequency of the major allele (1-MAF) x (1-MAF), and add together both homozygous results plus the heterozygous results, and check that it equals 1.0 (100%).

    So if MAF is 0.02 (2%), then being homozygous for the minor allele is 0.0004 (0.04%).
    Heterozygous is 0.0392 (3.92%).
    Homozygous for the major allele is 0.9604 (96.04%).
    So the total is 96.04% + 3.92% + 0.04% = 100.00%.

    The actual prevalence of genotypes (such as is shown on dbSNP near the bottom of the page for each SNP) tend to stick to this distribution quite closely. For example, if you go to http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs10776792 and look at the ESP_Cohort_Population subgroup (4550 alleles), the MAF is listed as 0.021, which should result in 0.0441% with AA for that group, 4.1118% with AG, and 95.8441% with GG. Actual distribution is 0.01% AA, 4.0% AG, and 96.0% GG, obviously with a bit of rounding in there somewhere :p
    Last edited: Jan 8, 2014
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  16. SickOfSickness

    SickOfSickness Senior Member

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    Thanks! That example really helps.
  17. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    My brain hurts! I'll leave the stats to you mathsy folks - my older brother got all the maths genes in my family. (Yes, I know it's not scientific but it certainly seems that way.)
    Valentijn likes this.
  18. madietodd

    madietodd Senior Member

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  19. SickOfSickness

    SickOfSickness Senior Member

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    Find the many colored lines and find the second and third that say European. The middle column shows in different colors which alleles they have. The second European line says
    0.0420.5000.0420.208 0.208
    The key is at the top of that column. Each color meaning a different one (orange is 0/G, dark blue means G/G, etc).
    The numbers are the percentages. Orange is 4.2%, the next is 5.0%, etc.
    The key has 6 colors and that sample group had nobody with pink so that's why the empty space for 0.0%.
    madietodd likes this.

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