Genetic SNPs Poll

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.

 

It sure is! I have trouble even reading my data, much less copying it snp by snp.

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.

 

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.

 

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...

 

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

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

 

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

 

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

 

...don't forget to control for ethnicity too, when you get round to your PhD thesis!

 

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.

"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."

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.

 

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.

 

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 Using data from a specific ethnicity would also be arbitrarily exclusionary toward non-Europeans, and I far prefer an inclusive approach.

 

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.

 

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]

 

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

 

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

 

Thanks! That example really helps.

 

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.)

 

Sadly, it just gave me a headache. I don't understand a single thing on that page.

 

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%.