My Promethease: No wonder I am confused

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drae
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My Promethease: No wonder I am confused

Postby drae » Fri Mar 16, 2018 7:58 pm

It has been one week since I heard back from 23andme. Saturday I made it through Promethease. Since then I have been trying to read. Please help by telling me what I've got here in words I will understand. Apparently Promethease is not sure 23andme is right about me having one copy of apoe4. Thank you!

Drae

Gs189
Gs189
Magnitude 2.5
Repute
Summary Probably ApoE E2/E4, but maybe E1/E3. E1 is the 'missing ApoE allele'
Criteria Gs189/criteria

Numerous people have now confirmed seeing this with no apparent consequences. It is interesting, but doesn't seem worrisome.

[PMID 17244188] This genoset looks for the possibility of ApoE1 'the missing APOE allele'. It is unclear why ApoE1 is rare. You have rs429358(C) and rs7412(T), but we cannot tell if they are in the same phase.

However we've still never had a gs267 report in. So it seems increasingly likely that you're E2/E4 and that E1 is really really rare.


The 'missing allele' ApoE1 is visible on the top strand. The bottom strand shows an ApoE3

The top strand is an ApoE2. The bottom strand is an ApoE4
This reference says that the rare APOE has been seen a few times before. In the paper, the person who had the rare APOE variant had ALS, Lou Gehrig's disease! Half of the others with the variant did not seem to have a severe disorder, while the others did. But they are talking about very small numbers.

There is also large bias, because healthy people weren't being sequenced much in 2007. The 4 people who've seen gs189 in their Promethease are completely healthy. Even if you're not healthy, it's unlikely that gs189 contributes to what ails you. gs189 highlights a mystery of all human genomes. Hopefully soon we'll learn more about this, and you may be one of the ones who can help us to answer the question. Whether or not you have it, there does appear to be a rare genotype, and you're one of the small number of people who can provide unique data. As you learn more please update this page.
I'm assuming I would need a more advanced genome scan to find out, that is, if there are not nice SNP's already measured on the 23andme chip that would help determine if I am E2/E4 like 23andme says, or E2/E3/unnamed?

It is possible other nearby snps could help to indicate the phasing of your data, but currently we've no further information.
How would I find out if I have the unusual variant?

You only want to know the full sequence of one gene, so you don't need a full genome scan. This type of work would cost less than $1000 to perform in a traditional lab, often MUCH less. While they probably exist, I'm uninformed on labs which are sufficiently 'consumer oriented' for your needs. If you're inclined, Yahoo answers has information on sequencing yourself, and perhaps the DIYbio community would be able to provide more information and resources.
There is also some discussion in this 23andMe forum post

Previously also known as gs143 the duplicate names were accidental and have been consolidated
Drae -- floundering forward, everlasting beginner.
Poco a poco. it don't work if you don't do it.
JulieG: Sticking with it slowly.
G.K. Chesterton: Practice makes progress.
A thing worth doing well is worth doing badly at first.

Anna
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Re: My Promethease: No wonder I am confused

Postby Anna » Fri Mar 16, 2018 8:31 pm

Wow, that's really interesting. My interpretation is that Promethease believes your result is 2/4, but 1/3, which is exceptionally rare, cannot be ruled out entirely. Honestly, I think this is good news since E2 is associated with reduced risk for AD.

What did 23andMe say your 4 was paired with? Was it just a missing result? Have you contacted them for their interpretation?
~Anna
4/4 but so much more

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drae
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Re: My Promethease: No wonder I am confused

Postby drae » Fri Mar 16, 2018 9:42 pm

Anna wrote:Wow, that's really interesting. My interpretation is that Promethease believes your result is 2/4, but 1/3, which is exceptionally rare, cannot be ruled out entirely. Honestly, I think this is good news since E2 is associated with reduced risk for AD.

What did 23andMe say your 4 was paired with? Was it just a missing result? Have you contacted them for their interpretation?


Thanks, Anna. I guess that is what I was thinking but it just didn't seem possible. 23andme said they could not tell what it was paired with. I have always been in one tail or the other of every bell curve.

What really confused me was 23andme led with the *bad* news about LOAD and then Promethease said
...no apparent consequences. It is interesting, but doesn't seem worrisome.


I'm not sure what to think.

Drae
Last edited by drae on Fri Mar 16, 2018 10:09 pm, edited 1 time in total.
Drae -- floundering forward, everlasting beginner.
Poco a poco. it don't work if you don't do it.
JulieG: Sticking with it slowly.
G.K. Chesterton: Practice makes progress.
A thing worth doing well is worth doing badly at first.

Anna
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Re: My Promethease: No wonder I am confused

Postby Anna » Fri Mar 16, 2018 10:02 pm

drae wrote:I have always been in one tail or the other of every bell curve.
I can relate to that!


I'm sure it is a bit unsettling to have such an ambiguous result. I have no idea why that can happen, but maybe 23andMe can shed some light on the situation or let you send in another sample.

I have a Promethease result for a different "bad" gene that Promethease says is a 23andMe error: miscalled by 23andMe, but otherwise indicates being a carrier of a phenylketonuria mutation. For 23andMe users this genotype most commonly occurs as the result of a genotyping error in their testing platform. I have no idea how Promethease would know this is a mistake.
~Anna
4/4 but so much more

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drae
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Re: My Promethease: No wonder I am confused

Postby drae » Fri Mar 16, 2018 10:11 pm

LOL Should my signature file be changed to:

Probably ApoE E2/E4, but maybe E1/E3


Does this mean I'm *special?* :roll:

Drae
Drae -- floundering forward, everlasting beginner.
Poco a poco. it don't work if you don't do it.
JulieG: Sticking with it slowly.
G.K. Chesterton: Practice makes progress.
A thing worth doing well is worth doing badly at first.

NancyM
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Re: My Promethease: No wonder I am confused

Postby NancyM » Sat Mar 17, 2018 6:22 am

I got the exact same results from 23&me/Promethease. Before doing that though I had already gotten my results from the Boston Heart test which determined I am apoe2/4. Furthermore, all four of my children have been tested through 23&me/Promethease and two were determined to be apoe2/3 while the other two are 3/4. Because my husband is 3/3 this confirms my 2/4 status. E1s are extremely rare and aren’t even mentioned in most literature so my conclusion would be: welcome to the 2/4 club! And yes, from everything I’ve learned, that little 2 could be providing us with some protection against the downsides of E4!

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drae
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Re: My Promethease: No wonder I am confused

Postby drae » Sat Mar 17, 2018 10:34 am

NancyM wrote:I got the exact same results from 23&me/Promethease...


Thanks, Nancy. Your story on this is nice to know. Perhaps time will confirm mine. I think I will accept the fact that I must be 2/4 and move on. Now I will try to make sense of the rest of the Promethease apoe stuff. Poco a poco.

I must remember to keep my focus on the protocol "doing" and not get too distracted researching this stuff. Today I need more research on reversing insulin and at least one basketball game. =)

Gotta go walk...

Drae
Drae -- floundering forward, everlasting beginner.
Poco a poco. it don't work if you don't do it.
JulieG: Sticking with it slowly.
G.K. Chesterton: Practice makes progress.
A thing worth doing well is worth doing badly at first.

ncjlhp
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Re: My Promethease: No wonder I am confused

Postby ncjlhp » Sun Mar 18, 2018 7:17 am

I also have that result from Promesthease and have been confused, but given my family history with AD I knew I had to have APOE4. My question about the APOE2 copy is does it really provide any real protection or is the APOE4 truly dominant/semi dominant? Studies tend to lump 4/2, 4/3, and 4/4 ( not all studies) together, leading me to believe that APOE4 is the more expressive allele (or just the one of interest to the study). I am also new to this, so I am still negotiating my way around the studies and the information offered on this forum ( which is excellent, BTW). I also wonder if my mother, who had a particularly severe course of AD (compared to my grandmother), was more likely to be 4/4 but since lifestyle is so key to the progression of the disease, I am not sure if that is even relevant. I will likely never know this, but I do wonder. My brother was also tested by 23 and me but is not revealing his status to anyone ( I do not blame him) but it would be good to know- another piece of the puzzle.

Harrison
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Re: My Promethease: No wonder I am confused

Postby Harrison » Sun Mar 18, 2018 8:11 am

It's unfortunate that Promethease has been causing so many problems with interpretation of E2/E4 vs E1/E3. The fact of the matter is that E2, E3, and E4 make up over 95% of ApoE genotypes, and it is highly, highly unlikely that someone would carry the E1 isoform.

Regarding E2/E4 and AD risk, there is some thought that the E2 "cancels out" the risk of E4, although the number of E2/E4 carriers has made this somewhat difficult to quantify. If one one looks at the percentage of the genotype that develops AD, E2/E4 tends to be somewhere between E3/E3 and E3/E4. We tend to forget that ~ 40% of Alzheimer's disease cases are E3/3 (and maybe a few E2/E3), and that the strategies that we focus on here to prevent AD are likely to be of use regardless of genotype.

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Re: My Promethease: No wonder I am confused

Postby Ades81832 » Tue Feb 05, 2019 11:56 am

Hi, I’m 37 years old, My 23 and me report says APOe4/e4 But Prometheus report say E1/E4. So is that even worse than E/4 E/4. Or even more ancient? Or possibly better?I had a higher percentage of neanderthal dna as well. I’ve always had lower HDLs but everything else is normal. I gained a ton of weight when I was pregnant. 3 times. Like 80 pounds? I don’t think I ate too much more, it was very strange. Normal HDLs through pregnancy.


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