Any updates on rs2075650 with APOE4/4 + family history?

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Nords
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Any updates on rs2075650 with APOE4/4 + family history?

Postby Nords » Sat Apr 10, 2021 9:09 am

I’m curious whether there’s new information on rs2075650 and its correlation with Alzheimer’s.

My spouse and I got our #2 Pfizer COVID-19 shots last week (no significant side effects). As part of that discussion, a friend forwarded a 2020 press release about a correlation between immunizations and Alzheimer’s.
https://www.alz.org/aaic/releases_2020/vaccines-dementia-risk.asp

It’s mostly a pitch for more studies (funding) of whether regular influenza & pneumonia shots help stave off dementia, or if that’s only a correlation in search of a causation. If you’re getting regular vaccinations then you’re probably also leading a healthier lifestyle that could offset your genome. I’m not holding my breath for an Alzheimer’s vaccine, and I’ll keep working on lifestyle.

Yet that call for more data reminded me that I’m carrying the rs2075650 G:G allele along with my two APOE4s. There’s also family history: my father developed Alzheimer’s in 2008 at age 74 and died in 2017. His father developed dementia in 1984 (age 80) and passed away in 2002. Of course my adult environment is far different than theirs but our genes aren’t helping.

It’s been a few years since the forum’s last thread about rs2075650. Here’s the most recent ones that I’ve found:
https://apoe4.info/forums/viewtopic.php?f=4&t=5371
https://apoe4.info/forums/viewtopic.php?f=16&t=4226&p=49672&hilit=rs2075650#p49672
https://apoe4.info/forums/viewtopic.php?f=2&t=4354
https://apoe4.info/forums/viewtopic.php?f=33&t=4668

I’m wondering if any studies since 2018 have changed the statistics on rs2075650. The reason I’m asking is that the 23andMe probabilities around APOE4 have consistently dropped for my European ancestry over the last eight years as they’ve gained more data on African-Americans, Hispanics, and Asians. There may be similar doubt cast on rs2075650 as more data is collected.

Has anyone seen more recent info on rs2075650 and its impact on Alzheimer’s probabilities?
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Re: Any updates on rs2075650 with APOE4/4 + family history?

Postby floramaria » Sat Apr 10, 2021 3:07 pm

Nords wrote:I’m curious whether there’s new information on rs2075650 and its correlation with Alzheimer’s.

Has anyone seen more recent info on rs2075650 and its impact on Alzheimer’s probabilities?

I recently saw a slide in a genetics presentation showing that a Meta-analysis of studies indicate rs2075650 may increase AD risk by 4X. Important to support mitochondrial membrane health.
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Re: Any updates on rs2075650 with APOE4/4 + family history?

Postby Nords » Sun Apr 11, 2021 9:37 am

floramaria wrote:I recently saw a slide in a genetics presentation showing that a Meta-analysis of studies indicate rs2075650 may increase AD risk by 4X. Important to support mitochondrial membrane health.

Thanks, Floramaria, I think that's what the number was back in 2018 too.

Maybe that SNP isn't getting the same attention for statistical analysis the way that APOE4 has.
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Re: Any updates on rs2075650 with APOE4/4 + family history?

Postby floramaria » Sun Apr 11, 2021 10:27 am

Nords wrote:Thanks, Floramaria, I think that's what the number was back in 2018 too.

Maybe that SNP isn't getting the same attention for statistical analysis the way that APOE4 has.
Yes, you may be right about that. I did a little poking around the internet and saw a Nov 2020 Meta-Analysis, but not any links to new research.
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Re: Any updates on rs2075650 with APOE4/4 + family history?

Postby NF52 » Sun Apr 11, 2021 6:38 pm

floramaria wrote:
Nords wrote:I’m curious whether there’s new information on rs2075650 and its correlation with Alzheimer’s.

Has anyone seen more recent info on rs2075650 and its impact on Alzheimer’s probabilities?

I recently saw a slide in a genetics presentation showing that a Meta-analysis of studies indicate rs2075650 may increase AD risk by 4X. Important to support mitochondrial membrane health.

Here's some more hopeful news: It all depends on whether you have ApoE 4/4:
In this genetic association study of the Alzheimer’s Disease Genetics Consortium imputed genotype at data, 14 415 variants near APOE (±500 kilobase) for 18 795 individuals with European ancestry were tested for association with AD using 4 logistic mixed models adjusting for sex, cohort, population structure, and relatedness. Model 1 had no APOE adjustment, and model 2 adjusted for the count of ε2 and ε4 alleles. Model 3 was restricted to ε3 homozygotes, and model 4 was restricted to ε4 homozygotes. Data were downloaded from May 31, 2018, to June 3, 2018, and analyzed from November 1, 2018, to June 24, 2020....rs2075650 was nominally associated with AD among the ε4 homozygotes (OR, 1.33; 95% CI, 1.00-1.77; P = .047).


https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2772020
Note that "nominally" doesn't mean "statistically significant association". The Odds Ratio is 1.33 which means (I think) that the TOMM40 SNP increases the risk for ApoE 4/4's by 1/3, which doesn't sound good--except that the Confidence Interval (likely score if replicated on a larger sample) is between 1.00 (no increases risk) and 1.77. And the P value is only 0.47. Which suggests that there is a 47% chance that these results would not be statistically significant, I believe.

So I call that not too bad. FWIW, you can search using the SNP on Google Scholar and get lots of recent articles.
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Re: Any updates on rs2075650 with APOE4/4 + family history?

Postby Nords » Sun Apr 11, 2021 9:26 pm

NF52 wrote:Note that "nominally" doesn't mean "statistically significant association". The Odds Ratio is 1.33 which means (I think) that the TOMM40 SNP increases the risk for ApoE 4/4's by 1/3, which doesn't sound good--except that the Confidence Interval (likely score if replicated on a larger sample) is between 1.00 (no increases risk) and 1.77. And the P value is only 0.47. Which suggests that there is a 47% chance that these results would not be statistically significant, I believe.

So I call that not too bad. FWIW, you can search using the SNP on Google Scholar and get lots of recent articles.

Thanks. It looks like there's a lot more data to be gathered before I'd add that to my list of things to consider.
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Re: Any updates on rs2075650 with APOE4/4 + family history?

Postby Jlhughette » Tue Apr 13, 2021 9:26 am

What about A/G? I’ve only seen G/G mentioned as a risk factor with rs2075650.
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