23 and Me Kit Information

[ShirleyP]

Hi,

I just purchased the 23 and Me genealogy version of their kit hoping to use the raw DNA from there with Promethease. I did the same thing with Ancestry, but they don't test for APOe4. Just wondering if this basic kit will work in the same way, or if I need to get the Health version?

My Ancestry raw DNA revealed that I do carry late onset Alzheimer's SNPs - rs 4420638 (GG) which is a proxy for APOe4. Does that mean that I am APOe4? I also carry rs 2075650 (GG) on TOMM40 which increases the risk for late onset Alzheimer's 4x more than usual.

It is in our family too with my father, his mom, and my maternal grandfather had it as well, although he had Parkinson's, and I don't think that they recognized that there is a dementia with Parkinson's back then (he passed away in 1994).

After reading Dr. Bredesen's book, and using Promethease, it's been a real education for someone with no background in genetics! Really interesting though.

Thanks for your help with my questions,
Shirley

[notmygenes56]

Hello,
I am not an expert but have looked at my reports and believe that the two genes they look at to determine status are rs7412 and rs429358. This article here gives a table (Table 2) on how your APOE status is determined using these 2 genes.
https://www.gbhealthwatch.com/GND-High- ... l-APOE.php
I hope this helps.

[Lucy5]

Hi notmygenes56 and welcome to our community!

I see you're already participating in our forum discussions and may have had a chance to being reading our site Primer written by a member physician. If not, we highly recommend it as a great place to start. It's an excellent and comprehensive source of information about the ApoE4 gene found in one place. We also have a Wiki with additional information located along the top of the page, as well as a Search function accessed by clicking on the magnifying glass icon also on the upper right of this page.

If at some point you'd like to introduce yourself and share a bit about what brought you to our site, the Our Stories forum would be the perfect place to post.

It the meantime, notmygenes56, looking forward to hearing more from you on the forums!
all the best..Lucy

[notmygenes56]

Thank you for the welcome Lucy5. I am just lurking around right now. I hope to get around to tell my story when I have a bit more time.

[ShirleyP]

Hi notmygenes56,

Thank you for your reply. The reference that you sent was excellent. Yes, it will be very helpful.

This is what I have found on several sites:

•PMID 17192785] The researchers found that on testing DNA samples from 1,086 well-characterized Alzheimer's disease cases, a single SNP (rs4420638) lying 14 kb distal to the ApoE locus has a powerful association with late-onset AD (corrected p value was 5.3 x 10 e-34). No other SNP showed as robust an association. The authors estimated that people with two ApoE-ε4 copies (i.e. presumably indicated by having either the rs4420638(G;G) or rs429358(C;C)genotypes) have a 25-fold increased risk for developing the disease compared to Apo-ε3/Apo-ε3 carriers.

That is what has shown up on Promethease using the Ancestry raw DNA. Ancestry doesn't share all of the APOEe4 information, so I am going to try to find out by using the 23andMe kit. I am rs4420638(G;G), but want to be sure. They also say that with the Ancestry raw DNA everyone shows up as (T;T) for 429358, even if they aren't - and I did too. They don't report anything for rs7412. Anyway, the kit is in the mail and I should know for sure soon. Then it will be a matter of making a few lifestyle changes beyond what I do already - it's going to be really hard.

[notmygenes56]

PMID 17192785] The researchers found that on testing DNA samples from 1,086 well-characterized Alzheimer's disease cases, a single SNP (rs4420638) lying 14 kb distal to the ApoE locus has a powerful association with late-onset AD (corrected p value was 5.3 x 10 e-34). No other SNP showed as robust an association. The authors estimated that people with two ApoE-ε4 copies (i.e. presumably indicated by having either the rs4420638(G;G) or rs429358(C;C)genotypes) have a 25-fold increased risk for developing the disease compared to Apo-ε3/Apo-ε3 carriers.

Thank you so much ShirleyP for that information. I learn something new every day from this site. I did a quick lookup on my Promethease Report and was relieved that on rs4420638 that I am AA which appears to be "normal/average risk for Alzheimers". I am thinking that this is good news. I am APOE 3/4. I have an 88-year-old mother who is also APOE 3/4. I looked up rs4420638 on her report and she is also AA. My mother shows no signs of cognitive decline. She is as sharp as a tack. I have been watching her very closely, seeing how she eats and lives her life because whatever she is doing, she seems to be averting any signs of developing AD.

I think you will find that your 23&Me raw data will give you all the information that you need to run through Promethease. The new 23&Me chip that they introduced last Fall does not report on certain SNPS, but I think you will find that in regards to APOE status and other relevant SNPS that they are adequate. Good luck and I hope that you get the information that you need.

[NF52]

I also carry rs 2075650 (GG) on TOMM40 which increases the risk for late onset Alzheimer's 4x more than usual.

The authors estimated that people with two ApoE-ε4 copies (i.e. presumably indicated by having either the rs4420638(G;G) or rs429358(C;C)genotypes) have a 25-fold increased risk for developing the disease compared to Apo-ε3/Apo-ε3 carriers. https://www.snpedia.com/index.php/APOE

Hi ShirleyP and notmygenes56,
Looks like you are both interested in the world of SNPs, which are the subject of considerable study by researchers all around the world. I think it's important to realize that finding that SNPs are associated with a disease does not necessarily mean that they cause that disease, or that they multiply the risk of other alleles which are associated with a disease.
The reference that you quoted from snpedia, that claims a 25-fold increased risk of developing Alzheimer's disease (AD) for Apoe 4/4 vs. Apoe 3/3 is from January 2007, Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database.
In genetics research that data is like having a 2007 cell phone. A "25-fold increased risk" would mean that If people with ApoE 4/4 had a 100% chance of getting AD (which they don't), then lucky Apoe 3/3's have only a 4% chance. If, as is more likely, people with Apoe4/4 have a 30-55% risk of EITHER mild cognitive impairment or Alzheimers by age 85, then that would mean someone with Apoe 3/3 has a 1.2-2.2% chance of having Alzheimers.

The truth is that somewhere between a large minority (45%) and a majority (70%) of people between the ages of 60 and 75 now alive with ApoE 4/4 will NOT get either MCI or AD before they die from something else. And about 10-15% of people with Apoe 3/3 will get MCI or AD. The results are almost certainly going to be better for younger people who will have the benefit of lifestyle interventions and possibly preventive medications.
APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts

As for the risk that you Shirley, might have an added 4x the risk of AD from that TOMM 40 GG SNP:
Here's the summary of meta-analysis published in 2015 that looked at the association between the TOMM 40 GG SNP and AD. After studying 4290 cases 0f AD and 5556 healthy individuals, the most they can say is that the results are "inconsistent" and there "may" be an association. That doesn't even prove an association with TOMM 40 and AD, much less that it adds to the risk of ApoE 3/4.

The association between the TOMM40 rs2075650 polymorphism and Alzheimer disease was examined by overall odds ratio (OR) with a 95 % confidence interval (CI). We used different genetic model analysis, sensitivity analysis, and assessments of bias in our meta-analysis.
RESULTS: The pooled analysis showed the inconsistent results that TOMM40 rs2075650 polymorphism was associated with Alzheimer disease in European and Korean population in all genetic models, but there was no significant association between the TOMM40 rs2075650 polymorphism and Alzheimer disease risk in Chinese population.
CONCLUSION: We conclude that rs2075650 in TOMM40 gene may increase the risk of Alzheimer disease.

[Emphasis added.]
Meta-analysis of the rs2075650 polymorphism and risk of Alzheimer disease.

A "rule" I try to follow in reading articles on individual SNPs and risk: Don't believe studies of small groups of people, or people in one geographic area. (Even if I'm glad that young men in Denmark with a SNP I carry do well on Wellbutrin for anxiety.) Instead look for recent articles and meta-analyses.

Don't sweat the big risk statistics: no one can tell you what YOUR risk is based on people who may have been misdiagnosed as having AD and were born around the time of your grandparents. Focus on making healthy choices in food, exercise, sleep and stress reduction and you will reduce many of the risk factors without reading any articles.

[notmygenes56]

Thank you NF52 for all of your information and informative links.

"Focus on making healthy choices in food, exercise, sleep and stress reduction and you will reduce many of the risk factors without reading any articles."

This quote is the most important take of it all.

[ShirleyP]

Hi NF52,

Thank you for all of that information. I have noticed that results are from a lot of different time periods, so it's confusing researching online when genetics isn't your field. What you have said helps a lot. It is good to see that the odds of developing dementia aren't as great as what they seem when doing online research.

I am looking forward to reading about more success stories and preventative lifestyle measure from contributors on this forum.

Thanks for your help and clarification,
Shirley

[NF52]

Glad to help Shirley! This is a place where it’s safe to ask anything, we’re all learning from each other and our own experiences, and we’re all paying forward the support we’ve received.