rs1129844 This story is so big... it deserves its own thread!

[J11]

rs1129844

I mentioned this SNP in the Exome Scan has Arrived! Help!! thread on a July 15, 2015 post.
Recently the result has been published.


http://www.sciencedaily.com/releases/20 ... 140757.htm
http://www.nature.com/mp/journal/vaop/n ... 5131a.html

This could be an important result for many on this forum: Delaying onset of AD by 10 years !! could mean everything.
Maximizing the benefits of eotaxin could be helpful for a wide range of people.

I am quite disappointed, though that confirmation of this result in say 44s, 34s etc. might take months or even years!
We really need a free standing database somewhere that has open access to medical records. Perhaps some nation
(e.g. the UK {they are really progressive about genetics}) could give their citizens an opt in clause that would allow for
their genome scans, clinical results etc. to be uploaded onto an open anonymized basis to the web.

If this were to happen someone, say me, in the comfort of my own hot tub could call up a sample of 1000 44s and compare age of
onset on the basis of the presence or absence of the minor allele of rs1129844. This could sure accelerate the pace of research. As it is, whenever a researcher wants to show anything, it almost always seems necessary to start from scratch. An open database would level
the playing field.

Such a database could give us immediate answers to the many important questions that now remain for rs1129844. Many
on this forum now have a substantial interest in what future research will determine about this SNP.

[Teezer]

Alright! A/G is the good combo, and I have it.

The above links didn't work for me, but SNPedia has it...

[J11]

Yeah, I am sorry I should have been clear about that rs1129844 AG is the good one. I am not sure about the AA genotype.

Nailing this one down would sure mean a lot to quite a few people on this thread. Say $50,000 per year for ten years in a nursing home.
So, that starts to move into real money. We are all just going to have sit tight for a while and let this all sort itself out.

It would sure be nice if this were more solid. It all seems too easy. The Colombians are probably fairly homogenous, so there might be other pluses and minuses lurking around in other populations, though rs1129844 did replicate in a LOAD population.

IGAP had almost 100,000 people and about all they found were SNPs that increased risk by at most 10%. This rs1129844 could have real impact on future planning for dementia caregiving needs.

[J11]

Ok, for the question about how to find the genotype on 23andme. It appears that the super duper new v4 23andme genechip does not have rs1129844, while the model T driving on the country lanes v3 genechip does.


One possible workaround for a no call would be to use the url below. This would impute your genotype for rs1129844.

Below is the output for rs1129844.
So, rs17735961 should be a perfect proxy for rs1129844.

rs3091237 is also on my genechip though it is not a perfect proxy.

My readouts for the two SNPs correspond correctly.
I think I am on v3, so i am not sure whether v4 has rs17735961.
Can anyone verify whether v4 has rs17735961?


SNP Proxy Distance RSquared DPrime Arrays Chromosome Coordinate_HG18
rs1129844 WARNING Query snp not on any selected array
rs1129844 rs17735961 554 1.000 1.000 I2,I5,I6,I6Q,IM,IMD,CYT,OQ,AxM,IWQ,OE,O24,O28,O54,O5E,OEE chr17 29636453
rs1129844 rs3091324 11978 1.000 1.000 AN,A5,A6 chr17 29625029
rs1129844 rs3091237 15091 0.938 1.000 I3,I5,I6,I6Q,IM,IMD,IC,ICQ,OQ,IWQ,OE,O24,O28,O54,O5E,OEE chr17 29621916
rs1129844 rs2368467 18048 0.938 1.000 ICA,ICB chr17 29655055
rs1129844 rs12601112 80999 0.878 0.937 A6,AxM chr17 29556008





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

[Russ]

GG here. Didn't win this lottery.

[Julie G]

Are we sure AG is the protective allele? Last time we talked about this, we suspected AA...

It might be that only carriers of AA genotype are protected (Only 2% of people have AA genotype). However, the small size of the add on study suggests that even a single A could help.

[J11]

Yeah, it is always a good idea to take the time to make sure everything is correct. I was confused as well because it seemed the original report was suggesting that this was somehow a rare mutation. The Colombian early onset mutation is rare, though the minor allele for rs1129844 is not really all that rare. 25% of people out there worrying about AD just got a nice big present under their tree from Santa!

HO!! HO!!
This is huge!

In AD there are not many large effect variants out there: APOE 4, TREM2, some rare PSEN1 and 2, APP, MAPT mutations,... and then rs1129844 which is a big positive for a lot of people!

"Although the gene mutation in the Colombian population is extremely rare, this variant is not," he added. "It occurs in about 30 percent of the population, which means it has the potential to protect a lot of people against Alzheimer's."

http://www.sciencedaily.com/releases/20 ... 140757.htm

[J11]

Below is our family readout from 23andme. The first column shows one family member. The 17735961 is a perfect proxy and it appears that a
C at rs17735961 equals a G at rs1129844, while an A at rs17735961 equals an A at rs1129844. The rs3091237 could also be used to impute
if necessary though the imputation would be less certain.

rs1129844 AG GG
rs17735961 AC CC
rs3091324 NA NA
rs3091237 CT CC

[Julie G]

Be still my ...first Klotho, now this? Thank you, J11. You are Santa Clause

[J11]

Ho! HO!

Why wait for Christmas?
We can have nice little presents all year round!

I am worried, though, as science often winds up being so much more complicated than that.
we will have to wait now possibly for years while this all gets replicated and re-replicated.

It was quite impressive, though that in the Colombians who were assured of devloping early onset AD that they were
protected by this allele. rs1129844 appears to offer powerful protection against AD. Would be great to see what might
happen if they could optimize its effects! Perhaps AD would then be delayed indefinitely!