Polygenic info used to identify risk of AD

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SusanJ
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Polygenic info used to identify risk of AD

Post by SusanJ »

They calculated estimates of risk for developing AD based on genotype (31 markers) and age, and tested it in two independent cohorts. Note it was primarily a European cohort. And yes, they list the snps, but not the risk allele. You'd have to dig that up.

Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score
http://journals.plos.org/plosmedicine/a ... ed.1002258
We found that the PHS [polygenic hazard score] strongly predicted age of AD onset within the ADGC Phase 2 dataset and the NIA ADC neuropathology-confirmed subset, demonstrating independent replication of our polygenic score. Within the NIA ADC sample, the PHS robustly predicted longitudinal progression from normal aging to AD, illustrating that polygenic information can be used to identify the cognitively normal older individuals at highest risk for developing AD (preclinical AD). We found a strong relationship between the PHS and increased tau-associated NFTs and amyloid plaques, suggesting that elevated genetic risk may make individuals more susceptible to underlying AD pathology. Consistent with recent studies showing correlations between AD polygenic risk scores and markers of AD neurodegeneration [22,23], our PHS also demonstrated robust associations with CSF Aβ1–42 levels, longitudinal MRI measures of medial temporal lobe volume loss, and longitudinal CDR-SB scores, illustrating that increased genetic risk may increase the likelihood of clinical progression and developing neurodegeneration measured in vivo.
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Re: Polygenic info used to identify risk of AD

Post by J11 »

Nice article!

It is somewhat frustrating though that no mention ever seems to be made of apoe33 dominant Alzheimer's. The risk alleles in the article have too small an effect to cause disease in a dominant pattern.

Three quarters of AD patients do not have an epsilon risk allele. Has there ever been a study that looked at those 33s with dominant illness? I would be quite surprised if somehow our families dementia was caused by some sort of a massively fluke of hitting hundreds or perhaps thousands of risk variants. And this could happen generation after generation?
Last edited by J11 on Sun Mar 26, 2017 8:02 pm, edited 1 time in total.
Sandy57
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Re: Polygenic info used to identify risk of AD

Post by Sandy57 »

Great point J11. We need to look at the 33 dominants as well.

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Re: Polygenic info used to identify risk of AD

Post by LG1 »

SusanJ wrote:And yes, they list the snps, but not the risk allele. You'd have to dig that up.
Ugh, can't someone do my homework for me? I'm deep into reading on cholesterol synthesis and also trying to refresh my chemistry so I can better understand biochemistry so I can better understand nutrition science so I can better know how to live longer and better. :)

If this is something really awesome, maybe we could split it up and each tackle a chance of the snp's?

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Re: Polygenic info used to identify risk of AD

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LG1 wrote:If this is something really awesome, maybe we could split it up and each tackle a chance of the snp's?
Here is the table. I started going through with the high P-values and found they are not in 23andme v4 chip, so I gave up.

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Re: Polygenic info used to identify risk of AD

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Harrison wrote:Here is the table. I started going through with the high P-values and found they are not in 23andme v4 chip, so I gave up.
Ha! I was just trying to copy and paste the table into a document, thanks.

I have my Promethease report but recently obtained my Genos report. Maybe I will have better luck. No idea.

Stay tuned.
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Re: Polygenic info used to identify risk of AD

Post by LG1 »

I just realized Genos searched my entire genome for variants but did not give me a file with my entire genome like I (perhaps naively) thought. I have only the variants they searched for... blah.

I turned up Zero from the table other than the apoe.
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Re: Polygenic info used to identify risk of AD

Post by Gilgamesh »

Harrison wrote:Here is the table. I started going through with the high P-values and found they are not in 23andme v4 chip, so I gave up.
Exactly what I started doing. LIke you, I discovered that none of the high impact alleles are on the v3 or v4 chip.

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Re: Polygenic info used to identify risk of AD

Post by Haslk »

LG1 wrote:
Harrison wrote:Here is the table. I started going through with the high P-values and found they are not in 23andme v4 chip, so I gave up.
Ha! I was just trying to copy and paste the table into a document, thanks.

I have my Promethease report but recently obtained my Genos report. Maybe I will have better luck. No idea.

Stay tuned.
Please let us know if the Genos report has these SNPs!
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Re: Polygenic info used to identify risk of AD

Post by Gilgamesh »

Laura, sorry if I'm being dense (highly likely!) but I don't understand this:
LG1 wrote:I just realized Genos searched my entire genome for variants but did not give me a file with my entire genome like I (perhaps naively) thought. I have only the variants they searched for.
By "searched for" I gather you don't mean sequenced, or do you? I thought their $499 service dumped a humongous exome scan result in your inbox, one with around 50 million SNPs. Not so? A full exome scan should have most if not all of the SNPs in this study. Did you get, or do you have access to, the humongous file?

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