Asking for my wife. She did Ancestry.com for genealogy. After much thought we ran it through Promethease. Result:
rs429358 = tt (that is 3/3) but
rs4420638=gg further genotyping was suggested this finding may serve as a proxy for APO E4
So she did a 23andMe. Result APOE 4/4 (rs429358 = cc ) Promethease says :
This variant is rare in the general population and it may be a miscall. If it is indeed a miscall, this variant's frequency based on its genotyping by 23andMe would be too high compared to what is expected in scientific literature, causing a false positive.
So she has discordant results. I think we need a third test. Which one would you use? Cost isn't the main issue but I doubt that insurance will pay.
That's really interesting. I don't know how to advise you, except that it's worth considering that your wife may not want the result in her medical record (a potential reason to avoid testing through a doctor).
I recently re-ran my 23andMe results through Promethease and noticed that they added that comment about it possibly being a miscall. I too am trying to decide what to do about it. I would of course LOVE my 4/4 result to be a miscall, but I was devastated by my initial Promethease report and am not sure I want to go through that again! I'm currently hanging onto the glimmer of hope that the 23andMe 4/4 result is wrong. My mom tested 3/4, and there is a lot of AD on my dad's side, so 4/4 fits; however, my daughter had an inexpensive test done through her fitness club that did not show any 4's.
I wonder how much higher the rate of 23andMe ApoE4 positives is compared to the scientific literature. I have been tempted to contact 23andMe and Promethease about this to see what they have to say but do not know how to do so without risking disclosure of my identity. If anyone has any further info, I'd love to hear it!
Hi Anna and Epsilon?,
This question of Ancestry calling a result ApoE 3/3 and 23& me calling it ApoE 3/4 or 4/4 has come up before. Here's a link to that thread from January 2018. epsilon 33, 34, 44 - whatever- what difference does it make????
By the way, it seems that Ancestry never says 3/4 when 23&me says 3/3. In fact, it seems that Ancestry rarely reports a 3/4 or 4/4 result.
From this comment by snpedia.com, it seems to be that Ancestry is not carefully checking ApoE status.
Word of caution to those with data from Ancestry.com: in our experience, based on data in OpenSNP and from Promethease users since 2006, Ancestry data always reports rs429358 as (T;T), even for people who's data from other sources indicates they are (C;T). Therefore, until Ancestry corrects this false negative problem, be aware that the ApoE genosets assigned by Promethease will be inaccurate when based on (inaccurate) Ancestry data. Specifically, some percentage of Ancestry users who are supposedly gs246 positive (Apo-ε3/ε3) are actually either gs141 (Apo-ε3/ε4) or gs216 (Apo-ε4/ε4).
For what it's worth, I and several people I know who have gotten our 3/4 or 4/4 results from 23&me had them independently verified as part of clinical trials. No one has ever been told "They got it wrong; you are a 3/3."
NF52 wrote:Hi Anna and Epsilon?,
This question of Ancestry calling a result ApoE 3/3 and 23& me calling it ApoE 3/4 or 4/4 has come up before. Here's a link to that thread from January 2018. epsilon 33, 34, 44 - whatever- what difference does it make???? . . . For what it's worth, I and several people I know who have gotten our 3/4 or 4/4 results from 23&me had them independently verified as part of clinical trials. No one has ever been told "They got it wrong; you are a 3/3."
Thanks NF52. I just skimmed through this thread. It definitely looks like Ancestry ApoE results should be questioned, and I was glad to see that SNPedia chimed in. I would love to see them do the same regarding the new Promethease statement about 4/4 possibly being a 23andMe miscall. Apparently, they believe that some people who verify independently will be told, "They got it wrong; you aren't 4/4."
FWIW, the 23andME 4/4 was correct for me . I independently verified through True Health Diagnostics. Epsilon?, did 23andMe not provide the results for rs429358 and rs7412 ? You can look them up yourself with the "Browse Raw Data" tool. If you have those, you can use this page to interpret.
FWIW, my 23andMe 3/4 (2nd in time) was confirmed through True Health (3rd in time) and LabCorp (did this test 1st). My wife confirmed her 23andMe 4/4 (1st in time) with True Health (2nd in time).
I had the exact same experience with Ancestry - Promethease warned that Ancestry always reports 429358 as T;T. I just received my results back from 23andMe last week and am ApoE 4/4. With a lot of family members with Alzheimers I am guessing that it is correct, and it is also what I was expecting.
Being from Canada the health insurance isn't a real issue for us here.
I was reading about a new test that is going to be available very soon through Dash Genomics "a test that calculates how more than two dozen genetic variants act together to increase or decrease your risk of developing the disease during your lifetime. They say it’s more accurate than current tests, which hinge on a single gene. It can also predict with some degree of confidence how old you’ll be when symptoms first arise. And in a few months anyone with access to a commercial spit kit will be able to get it."
I think that I've found out enough information without going that route at this point in life. Going to focus on preventative measures rather than dealing with that information which for me is "too much information".
Julie: The underlying report for the snps matched the E4 report for 23 and Me. I looked at the raw data report. It is all consistent with Promethease.
Anna: I'll ask Promethease. I was wondering if the excess E4 is due to a higher risk group taking the test compared to the general population.
NF52: Thanks, I searched but missed the previous thread. My wife did sign up for the trial process. She is willing to participate but we also thought this might be another way to confirm Apoe status.
Julie and Tincup: Thanks for the tip about Truehealth. It is blood based, right? We had been thinking about the LifeExtension test which is a cheek swab.
Julie and Tincup: Thanks for the tip about Truehealth. It is blood based, right? We had been thinking about the LifeExtension test which is a cheek swab.[/quote]
Yes, True Health & Labcorp are blood based.
You can order LabCorp through DirectLabs or Walkin Labs. It has a name that doesn't reference Apo E as I recall. I've posted on it elsewhere here. If you want it and can't find my prior post, ping me with a PM and I'll figure it out.
I have been confused as well. 23 and me called one APOE4 allelle, Promethease said E4/E2 or E3/1 and Ancestry said no APOE4. I figure I am really APOE4/2 because E1 is rare and it makes sense with my family history to be E4, but I haven't gotten it verified. I am just trying to live well and deal with it as best I can!
. I independently verified through True Health Diagnostics. Epsilon?, did 23andMe not provide the results for rs429358 and rs7412 ? You can look them up yourself with the "Browse Raw Data" tool. If you have those, you can use this 
