GG rs9472817 annuls APOE epsilon 4 risk? Wo Hoo!

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GG rs9472817 annuls APOE epsilon 4 risk? Wo Hoo!

Postby J11 » Sat Mar 05, 2016 7:28 pm

Just reported by J1 (no relation) on snpedia "the risk conferred by the APOE-ɛ4 allele was annulled in subjects with two copies of the G allele". This is only an initial report, might be wrong, though it sure gives you a lift. This might not apply to 44 carriers.

Not bad n size. "...Here we analyzed the variability of UCP2, -3, -4, and 5 genes in sporadic and familial cases (n = 465) of late-onset AD (LOAD) with respect to healthy controls (n = 442)."

Someone have access to this one? Would love to see what's under the hood?

I would want to make sure that the Cs and Gs are the right way around.
dbsnp is reporting MAF G=0.38.
Which way round does 23andme report reverse or forward?

http://www.snpedia.com/index.php/Rs9472817
Last edited by J11 on Mon Mar 07, 2016 9:22 pm, edited 1 time in total.

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Re: GG rs9472817 annuls APOE epsilon 4 risk? Wo Hoo!

Postby J11 » Sat Mar 05, 2016 7:45 pm

Did they really miss this one on IGAP?
It seems so hard to believe that there could be such apparently huge positives floating around out there
and everything had been so fixated on only finding bad news. We have seen this a few times already on the forum.

It might not ultimately pan out for this particular SNP, though it certainly does make one wonder why finding good news had not
been higher on the list of priorities.

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Re: GG rs9472817 annuls APOE epsilon 4 risk? Wo Hoo!

Postby SNPedia » Sat Mar 05, 2016 8:09 pm

When 23andMe reports on this SNP, it reports on the plus/forward/positive strand.

At a quick glance, though, this SNP is quite variably reported by 23andMe. It's possible (but we haven't had time to investigate this yet) that the newest 23andMe chip no longer contains this SNP, or if it does, it's under a "secret" i-SNP name.

Keep in mind the publication being cited is a first report and as such should be considered preliminary; it is certainly going to be studied by others, and although sometimes negative results are not published, if an independent group actually confirms this in an equal or larger population, it will get published.

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Re: GG rs9472817 annuls APOE epsilon 4 risk? Wo Hoo!

Postby apod » Sat Mar 05, 2016 8:18 pm

Looking on my 23andme data, I see:
Gene: SLC25A27, LOC100131283
Position: 46640992
SNP: rs9472817
Genotype: CC
dbSNP Orientation: Plus
dbSNP Genotype: CC

It sounds like that's the opposite of what I want to see?

Homozygote carriers of the C allele who were also carriers of epsilon 4 genotype were at double the risk of LOAD (Late onset Alzheimer's disease).
:|
Last edited by apod on Sat Mar 05, 2016 8:21 pm, edited 1 time in total.

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Re: GG rs9472817 annuls APOE epsilon 4 risk? Woo Hoo!

Postby J11 » Sat Mar 05, 2016 8:20 pm

I hit GG, (as reported by 23andme) on this, so it would amazingly awesome if this takes out my epsilon 4 risk.
This would be like a get out of jail free card. YEAH!

23andme's site is calling it C or G, though I want to be 100% clear what GG means. There can be a certain ambiguity with forward and back. Anyone cracked into the article? It would be almost beyond real if they are calling this as true for 44s as well
as 4s. At 38% MAF, so 15% of 44s might also have a get out of jail free card too, I think that would be somewhat optimistic: that would mean that this one SNP is almost single handedly releasing 44s from prison.

Yet, I do recognize the caveats, and often the first report overstates the benefit. (Winner's curse)

I am also liking this one. Hemodalysis anyone?
http://www.ncbi.nlm.nih.gov/pubmed/26923028
Last edited by J11 on Sat Mar 05, 2016 8:58 pm, edited 2 times in total.

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Re: GG rs9472817 annuls APOE epsilon 4 risk? Wo Hoo!

Postby Teezer » Sat Mar 05, 2016 8:22 pm

Hmmm. I show GG on rs9472817... :shock:

Can I go back to having a glass of wine after a meal, now? 8-)
It's weird how I'm constantly surprised by the passage of time when it's literally the most predictable thing in the universe. -- xkcd

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Re: GG rs9472817 annuls APOE epsilon 4 risk? Wo Hoo!

Postby Hubbs » Sat Mar 05, 2016 8:31 pm

I checked my 23&me raw data for rs9472817 but it says "not genotyped. :roll:
E3/E4
MTHFR compound heterozygous (C677T and A1298C)
A1c5.7/LDL-P1602
All advices appreciated :)

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Re: GG rs9472817 annuls APOE epsilon 4 risk? Wo Hoo!

Postby J11 » Sat Mar 05, 2016 8:38 pm

Well, this is a real life lesson for me in the importance of being careful with one's posts!
If everyone goes back to all of their old habits, then they might be in worse shape for future dementia than if they had had CC
genotype. And we do have to be careful about what GG actually means.

I am really pveed that we are now going to have to sit around for months perhaps years for confirmation on this one.
It makes no sense!
Governments have spent hundreds of millions of dollars ( pounds, euros ...) of our money and we have no database of any size
that we can go to right now and have some confirmation with a larger group of whether rs9472817 is for real or not. It is sooo wrong. There has to a few thousand people out there who would be willing to be put into an anonymous online publicly accessible Alzheimer gene chip database. We could answer the million dollar question instantly. Instead we are going to have to sleep lightly for the next while.

Hubbs maybe there is a proxy for it.
There is some uncertainly whether it is on the new gene chip platform.

Does anyone know how to add in a genotype to an rs page on snpedia?
Do you have to wait a few days for the computer to add in a box for it?
Last edited by J11 on Mon Mar 07, 2016 9:24 pm, edited 1 time in total.

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Re: GG rs9472817 annuls APOE epsilon 4 risk? Wo Hoo!

Postby J11 » Sat Mar 05, 2016 8:53 pm

Here's what the broad says about proxies.

http://www.broadinstitute.org/mpg/snap/ldsearch.php

SNP Proxy Distance RSquared DPrime Arrays Chromosome Coordinate_HG18
rs9472817 rs9472817 0 1.000 1.000 I6Q,IMD,IWQ,O54,O5E chr6 46748951
rs9472817 rs9381468 15718 0.967 1.000 IM,IMD,OQ,AD,OE,O24,O28,O54,O5E,OEE chr6 46733233
rs9472817 rs9381469 10924 0.904 1.000 I1,I6Q,IM,IMD,OQ,IWQ,OE,O24,O28,O54,O5E,OEE,AAH chr6 46738027
rs9472817 rs9296505 11151 0.904 1.000 AN,A5,A6 chr6 46737800
rs9472817 rs9296504 11487 0.904 1.000 A6,I3,I5,I6,I6Q,IM,IMD,IC,ICQ,CYT,OQ,AxM,IWQ,OE,O24,O28,O54,O5E,OEE chr6 46737464

Snpedia is not listing any of the above proxy snps.

Anyone know how to edit a title for a thread?
The Woo Hoo for the thread title is missing an o in the Woo!

If this one pans out I will be Woo hoo ing quite a bit.
It would be embarrassing if the title were missing an o!
Last edited by J11 on Sat Mar 05, 2016 9:02 pm, edited 1 time in total.

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Re: GG rs9472817 annuls APOE epsilon 4 risk? Wo Hoo!

Postby SNPedia » Sat Mar 05, 2016 9:00 pm

The genotypes are already in SNPedia.

Do you really feel the research meets the SNPedia criteria?

Our emphasis is on SNPs and mutations that have significant medical or genealogical consequences and are reproducible (for example, the reported consequence has been independently replicated by at least one group besides the first group reporting the finding). These are typically found in meta-analyses, studies of at least 500 patients, replication studies including those looking at other populations, genome-wide significance thresholds of under 5 x 10e-8 [PMID 25666886] for GWAS findings, and/or mutations with historic or proven medical significance.

And yes, we see that User:J1 has already gone ahead and added the summaries, but at least based on the abstract, the conclusions of this paper seem very preliminary. To cause even more worry for the ~15% of all e4 carriers who also happen to be rs9472817(C;C) doesn't seem thoughtful, even with a caveat that confirmation awaits a larger study.


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