GG rs9472817 annuls APOE epsilon 4 risk? Wo Hoo!

[LanceS]

I am a 4/4, so I may not have a "get out of APOE4 jail free card". Have the same 3 SNPs as Hubbs. I am just a newb when it comes to bio. Took me a while to fill in the gaps on this thread. However; I can tell you my body and mind feel so much better having spent a year or two trying to take better care and feeding of my mitochondria.

It may be that the "environmental factors" driving diabetes and obesity rates are affecting us all and that the CVD and brain issues raised by these factors could need addressing more than an APOE status. I don't have studies offhand but the health metrics that folks on this board hit are often times much much better than on overall studies where APOE4s fare so poorly. This clearly indicates that environmental factors have a big part to play in "awakening" the APOE4 risk within. Certainly this whole affair has awakened me to CVD issues that I desperately needed to address. Hopefully I live long enough to worry about the brain issues

Thanks for posting. Interesting discussion. Back to my ice cream

J/K

[Silverlining]

J11. I checked my father's v4 chip and he's homozygous for all three snps. So for the chart or table you're working on you could add my 4/4 father who is 75 yrs and myself 4/4, 51 yrs with the same snps. I see Lance above as a 4/4 has the same. So that's three 4/4's right here and probably more who haven't checked their dataset. Seems a somewhat common allele set? I've seen so many bad alleles, I'm fairly indifferent anymore. There was another post in the past few months, klotho maybe (?), that I had all the bad ones!

[BerniF]

I'm a 3/4 and am heterozygous for these three! Would have been nice to be homozygous

rs9381468 (GG) AG
rs9296504 (CC) CT
rs9381469. (AA) AG

[Thx4thegenes]

Same here BerniF. Heterozygous. Figures.

[Kathleen1]

I am 3/4
Heterozygous for all 3

rs9381468 AG
rs9296504 CT
rs9381469 AG

and for this thread as prior noted
rs9472817 CG

[J11]

Silverlining, your point is well taken about the apparent excess of GGs that have been reported. At GMAF 35%, we should only be looking at
15% homozygotes, while it appears that more than would have been expected have been posted to date.

One thing I noticed on dbsnp is that there is quite a range of frequencies across different ethnicities for this SNP.
For example, Asian frequencies actually push towards 60% (? dbsnp only shows up to 29% GG with 59% allele frequency
on a small sample, why are there 4 numbers in the table? What is HWP?) so the homozygotes would be around 35%.
http://www.ncbi.nlm.nih.gov/projects/SN ... rs=9472817


dbsnp really should update its allele frequency lists.
Instead of looking at a handful of genotyped individuals, the exac browser has for example nearly 120,000 for rs9381469.
Would have been great if they gave more details on genotypes by ethnicity.
http://exac.broadinstitute.org/gene/ENSG00000153291

And yes, it is quite impressive how easily we can find 44s on our site for feedback on this study.
In the present study it should not be entirely surprising to learn that no GG44s were included in the sample, and yet we already have 3!
BTW, Silverlining is your 75 year old GG44 father cognitively intact?

According to the study (assuming that GG works with 44s), he should be.
Given the expected age of onset of 44s, his being cognitively unimpaired would be unexpected.

Also wonder whether some on the forum could reconstruct the genotypes of their parents and possibly other
relatives to help work this through. For example, LanceS being GG44 means that both his parents carried at least a G4.
Perhaps with his own phased result (and other family members) it might be possible to work through the rest of the
817 genotypes of his parents.

Given the enthusiasm for this report (and the still substantial uncertainty surrounding its replicability) I think the forum
should endorse in principle the open science initiative of the Montreal Neurological Institute.
http://www.sciencemag.org/news/2016/01/ ... te-science

[Lucy5]

J11,

I go back-and-forth regarding cking further into my genetics...for me, too much bad news at once can be a little demotivating (and have me heading for the donut aisle . But I am a bit in awe of your dedication/knowledge on this subject and sometimes can't resist. I'm a 4/4 and my results below.
rs9381468 (GG)
rs9296504 (CC)
rs9381469. (AA)

[Julie G]

Whoa...I'm happy for all of my lucky friends!!! I'm still working the program waiting for my "get out of jail" card . I'm also in awe of your determination, J11. Thanks for sharing with us all.

[J11]

Lucy5, wow just amazing this forum is off the chart with GG44s. Amazing!
I am not sure whether the study had any, around here we just have to ask the 747s with GG44s to keep on circling
around, while we find a place on the runaway.

If we ask around we could probably find a fair sample of 44s at the age of AD onset to help us work through whether
GG really does work for 44s. It is not clear to me what the study implies for 33s. It is entirely possible that GG33 would
not be especially protective against AD.

At the same time, I do have certain misgivings about this entire exercise. It reminds me of those sociopsychological studies
where they invent a completely bogus indicator and all of a sudden people have internalized it as being real. We all have to remember
that this experiment has already been done 2973 times before and 2973 (according to alzforum) times the research was wrong ! It should surprise no one that 9472 is a near backward anagram of 2974.

Sure, I have to admit that when I saw my GG it was an immediate lift, as I suppose it must have been just as much an immediate drag for
those without a GG. Yet, those on this forum have chosen to live life knowing what the cards have dealt them and they want to play their hand wisely, given this knowledge. There are probably more than a few million Americans out there who not only do not know that they are carriers of an epsilon 4, but also that they have a GG which might annul the 4. Who, on the forum, would truly want to live their life so oblivious to the truth?

Something that those dealt a CG or CC should appreciate is that Uncoupling Proteins (UCPs) in mitochondria are already widely studied in cancer research and it would seem that even a CC could wish that this research will be replicated. This is because UCPs appear to be a scientifically accessible defect. There are likely an entire range of potential defects that once found might require decades of research to find a druggable target. With defective mitochondria, one simply wonders why not do a mitochondrial transplant?
If the current research is replicated, such a scenario would be an extremely favorable result for the CCs.

Furthermore, having insight into one's genetics might offer the opportunity to take advantage of one's specific biology to select personalized treatments. Otherwise, one will simply be treated with off the shelf therapies that work for the "average" person.

"It is envisioned that estrogen-induced ROS mediated signaling is a key congruent mechanism that drives the modulation of uncoupled proteins in papillary thyroid carcinoma cells. The present study investigates that estrogens may increase mitochondrial ROS production by repressing uncoupling proteins, which offers a new perspective on the understanding of why thyroid cancer occurs three times more often in females than in males, and the occurrence decreases after menopause."
http://www.ncbi.nlm.nih.gov/pubmed/26450681

[J11]

Hey Hubbs, I'm happy that you're happy!

This whole idea of sending out happiness to others is really taking hold of me.
There is a definite positive feeling when learning of the GG for 817, I noticed it and others with GGs are showing their ivory whites.

There might be a strategy here for engineering global happiness: accentuate the positives and relegate the negatives.
For snpedia, one could give the GG a 3.0 magnitude good and the CC a 2.0 magnitude bad.

In this way people could focus on their blessings!