rs2075650

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
Max100
Contributor
Contributor
Posts: 17
Joined: Wed Aug 31, 2022 8:19 am

rs2075650

Post by Max100 »

Anyone have insight on rs2075650?

I’m an E3/4 with A/G alleles which shows increased risk for Alzheimer’s, but have also read that G is linked to E4. Perhaps it’s common to have an E4 and G allele? Maybe 4/4 are commonly G/G and 3/4 AG? Another package deal or is it a separate risk factor?

Thanks for any insight!
Jgreg80
Contributor
Contributor
Posts: 12
Joined: Wed Feb 13, 2019 12:37 pm

Re: rs2075650

Post by Jgreg80 »

Usually a package deal, along with rs4420638.
Max100
Contributor
Contributor
Posts: 17
Joined: Wed Aug 31, 2022 8:19 am

Re: rs2075650

Post by Max100 »

Jgreg80 wrote: Mon Sep 26, 2022 8:45 am Usually a package deal, along with rs4420638.
So no added risk?

https://jamanetwork.com/journals/jamane ... ct/2772020

The article states:
The association between rs2075650 and AD was nominally significant among ε4 homozygotes (model 4) (OR, 1.33; 95% CI, 1.00-1.77; P = .047) but failed to reach significance after APOE adjustment (model 2; OR, 1.09; 95% CI, 0.99-1.19; P = .07) or among ε3 homozygotes (model 3; OR, 1.16; 95% CI, 0.98-1.38; P = .09).

When considering E4 status it seems to add no risk.
Max100
Contributor
Contributor
Posts: 17
Joined: Wed Aug 31, 2022 8:19 am

Re: rs2075650

Post by Max100 »

So having a G doesn’t increase risk, but an AA might reduce it?
Jgreg80
Contributor
Contributor
Posts: 12
Joined: Wed Feb 13, 2019 12:37 pm

Re: rs2075650

Post by Jgreg80 »

Probably not much, if at all. rs157580 is the TOMM40 SNP that is significantly associated.
Max100
Contributor
Contributor
Posts: 17
Joined: Wed Aug 31, 2022 8:19 am

Re: rs2075650

Post by Max100 »

Jgreg80 wrote: Mon Sep 26, 2022 9:21 am Probably not much, if at all. rs157580 is the TOMM40 SNP that is significantly associated.
Thanks for the feedback. I’m not finding much information with regards to rs157580 and Alzheimer’s risk other than it’s in the large risk pool of genes.

Does the A allele increase risk for E4 carriers or is the risk increase across 3 & 4? I’m a GA so curious as to the amount of increased risk? Thank you again!
Jgreg80
Contributor
Contributor
Posts: 12
Joined: Wed Feb 13, 2019 12:37 pm

Re: rs2075650

Post by Jgreg80 »

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727495/

I’m not sure exactly how the risk is stratified by genotype, but the A is protective.
Max100
Contributor
Contributor
Posts: 17
Joined: Wed Aug 31, 2022 8:19 am

Re: rs2075650

Post by Max100 »

Jgreg80 wrote: Mon Sep 26, 2022 10:32 am https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727495/

I’m not sure exactly how the risk is stratified by genotype, but the A is protective.
Thank you for the link and insight. So if I’m deciphering this meta analysis correctly, for caucasians AA very protective, AG somewhat and GG is indifferent so far as it doesn’t magnify risk?
Jgreg80
Contributor
Contributor
Posts: 12
Joined: Wed Feb 13, 2019 12:37 pm

Re: rs2075650

Post by Jgreg80 »

Depends how you look at it. One could say each G increases risk.
Max100
Contributor
Contributor
Posts: 17
Joined: Wed Aug 31, 2022 8:19 am

Re: rs2075650

Post by Max100 »

Jgreg80 wrote: Mon Sep 26, 2022 11:39 am Depends how you look at it. One could say each G increases risk.
Sorry for all the questions, but what’s the increase in risk with this particular TOMM40 gene? Didn’t see anything in the study. Are the G alleles part of linkage disequilibrium where 4’s typically have a G? Thanks again!
Post Reply