Advice? Support? Info?

[GeekyMum]

Background - sent off tests to 23andme last year, before the November health results shutdown. I was just looking for ancestral data. Absolutely shocked to learn that my teenage son was a 4/4, husband 3/4 and a no call for me. Have since had my (75 year old) parents tested. Looked through their raw data and determined that Mom is a 4/4 and Dad is a no call as well. Mom is showing signs of mild/moderate MCI, under the care of a neurologist, and recently begun Aricept. I've also got her started on coconut oil, but it's difficult as they are in another state.

I also had an ancestry.com DNA test run on me, and ran that raw data through Prometheus.com. Found nothing on rs429358 and rs7412 in that report either. What am I to make of that? I'm assuming I'm a 4/4 as well, but I'm not sure what to think.

Very down. Working hard to get my diet and exercise situation up to snuff. Both husband and son are fitness/health freaks, and look amazing.

[Silverlining]

Hi GM! I can only briefly post at this time. I am 4/4, my father is 4/4. I am 50 and female. My dad is 74 and doing well. You are at least a 3/4, but not necessarily a 4/4. I don't have the snp references with me. Someone else will chime in.

There are lifestyle changes you and your family can make to better your health now and for the future. Diet, exercise, judicious use of supplements, sleep hygiene and more. There is a LOT of good info here and good people. Take a few days or weeks to just breathe and recognize you can be proactive in this situation. Surf around our site, ask questions; as they say Rome wasn't built in a day. Mostly remember to stop and smell the roses . Oh and check out the thread relating to the MUSE study for E4's.

[J11]

There might be a way around these genotyping problems.

For example, there are a large number of SNPs in the APOE gene region that pick up on the signal.
Some of the research notes that some of the clearest signals for the risk in the APOE gene region actually occurs in the TOMM40 gene. You might be able to use those SNPs instead of the epsilon 4 locus.

Also, since you have genotypes from your close family members, you might be able to work out your genotype without even having all the information, you could impute your results. So for example, if you could determine phased chromosome 19s for your son and your mother, then if your son did not have a matching 19 chromosome with your mother then it must have come from your father. The only way that could have happened is if you inherited a 4 from your mother and father (meaning you are 44). However, if your son had a 4 from your mother, you would not be able to determine your genotype in this way. (Entire chromosomes can pass from parent to offspring. On average there might be 1 or 2 recombinations per chromosome. This means that the chromosomes that pass from generation to generation should have substantial regions of identity. If you phased the chromosomes, you would more easily see these similarities.)

I believe ancestry.com is very much up on analyzing genomes from this broader genomic perspective.
I am not entirely sure how you would go about what I have suggested, though there should be phasing software available on line.
Could some one help out here?

Don't be down about all this. It appears that effective treatments for Alzheimer's might finally be approaching. Biogen has reported very strong results. TauRx should be reporting within a year. Molecular Tweezers... The list goes on and on.

When the power brokers finally realized that Alzheimer's was too big to happen (just as the banks were too big to fail), a solution had to emerge. There is simply no possible way the world community could have managed the Alzheimer dementia crisis without
soon discovering effective anti-dementing drugs. America was heading toward a $1 trillion per eyar AD price tag with the nation's children enlisted as caregivers. Such a future would have been unbearable. When problems get too big, the community finally realizes that investing in solving the problem offers a good return. This is true of problems of any complexity.

The great tragedy is many problems are simply not deemed important enough to solve.

[GeekyMum]

Thank you for the replies, Silverlining and J11. I'm glad I know that I'm an APOE4, it's just all a bit overwhelming. I'm very much aware that I am now armed with this knowledge and can make more informed decisions about my diet, exercise and health care. I go to the grocery store now and look with a very jaundiced eye at all that prepackaged stuff.

J11, I wondered if I might be able to determine my status by looking at other snips. I will look into my son's and mother's 19s and see what I can find. I did get this from the Prometheus report, but I'm not sure what to make of it:

___________________________

3.23x risk for Alzheimer's disease

rs9886784(A;C)

s9886784, a intergenic SNP on chromosome 9, is reported to influence the risk for Alzheimer's disease based on a study of ~1100 Canadian patients. The risk allele is (A); the odds ratio is 3.23 (CI: 1.79 - 5.84).

And this:

2x higher Alzheimer's risk

rs2075650(A;G)

Located close to ApoE4, yet may independently (also) influence risk of Alzheimer's disease. A case-control study of 381 patients found a 2x higher risk for Alzheimer's disease associated with the rarer rs2075650(G) allele. This allele is associated with earlier onset of Alzheimer's disease, by ~7 years. (news) The data from this study are available online at The association of this SNP with late-onset Alzheimer's disease] was confirmed by a study reported in PLoS Genetics. The A allele of this SNP is one of 150 identified as relevant to exceptional longevity in Recent work suggests, however, that the linkage disequilibrium between rs2075650 and the ApoE ε4 defining SNP rs429358 means that there may be little, if any, independent effect of rs2075650 on Alzheimer's risk.

[Stavia]

Hi honey, welcome! Its a lot to get your head around. But there's no hurry. Please ask away.

[J11]

I find it very frustrating that snpedia and others make these claims that are flagrantly wrong.
I do not see how they could be possibly correct.

The best look at AD genetics was from the IGAP trial published in 2013.
None of the confirmed SNPs that were found in IGAP had an OR much more than 1.1.

http://www.snpedia.com/index.php/Alzhei ... %28IGAP%29


All of the studies before that claimed high ORs (e.g. 1.4 or higher) in SNPs not found in IGAP should now be
considered highly suspect.

Yet, the SNP in the APOE region could quite reasonably be valid. There are many SNPs in that region that pick up on the AD signal.


Our family has been trying for quite some time to understand why our loved one developed AD when their genotype is 33.
This passed from parent to offspring so there is likely to be a large genetic risk factor somewhere we have not been able to find it.

[J11]

Here's a possible work around for your trouble.

The large 2009 meta-analysis in AD found that the APOE region SNP rs2075650 (it is actually in the TOMM40 gene) was the most significant
variant in the region (p value =1.8x10-157).

This variant is thought to be picking up the signal from APOE. You could use this SNP as a substitute for epsilon.
For example, our loved one with dementia who genotyped epsilon 33 , genotyped AA at rs2075650 (rs2075650 is also on our version of the
23andme genechip. An offspring who genotyped epsilon 34, was genotyped AG. It seems A at rs2075650 is an epsilon 3 and a G an epsilon 4.)

The linkage information below does not confirm this idea, though this might simply because epsilon is made up of the pair of the SNPs together.

http://www.broadinstitute.org/mpg/snap/ldsearch.php
rs2075650 rs429358 16322 0.198 0.646 OQ chr19 50103781
rs7412 rs2075650 16460 0.015 1.000

APOE rs7412 and rs429358 form the APOE epsilon genotype.


Could other forum members compare their epsilon and rs2075650 genotypes to confirm this idea?

[KatieS]

I can confirm that 4 family members who are E3/4s also have rs2075650AG.

[J11]

Great!

Any 44s out there that could help out?

[Tincup]

2 family members are rs2075650(A;G) and 3/4. Another is rs2075650(G;G) and 4/4.