Genetic Architecture of AD: Update

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
J11
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Genetic Architecture of AD: Update

Postby J11 » Wed Oct 14, 2020 10:19 am

Great article! Will need to read the fine print, though, as they introduce a fair number of new concepts
to understand.

The article gives a good idea of where we are now in unraveling the genetic
architecture of AD. The snp heritability of AD is fairly low, yet it is still disappointing
to see how low the sample sizes and how close to little of this heritability has been found to date
(The blue dot to the above and to the left of the number 5 on the x-axis -- That's AD!! Right around 0?? Not sure
if that totally makes sense. Don't the current ~40 AD snps tell us anything?). The figure shows that
almost 100% of the genetics of snp AD heritability would be known at a sample size of ~5 million.
Yet, AD snp heritability is only ~8%. The contribution from apoe epsilon 4 is much larger than that
from other snps. It would be helpful if an updated population attributable fraction for known
AD snps were to be published.

Considering the improvement that would be possible in clarifying the genetic nature
of the illnesses shown in these figures it is not clear to me why larger studies have not been done.
Illnesses such as schizophrenia are moderately heritable and yet the research has not ramped
up as much as one might expect. With the imminent arrival of population scale full genome sequencing
perhaps We the People can push this over the line.


pgen.1008612.g003.jpg


pgen.1008612.g001.jpg



https://pubmed.ncbi.nlm.nih.gov/32427991/
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anotherdreamer
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Re: Genetic Architecture of AD: Update

Postby anotherdreamer » Thu Oct 15, 2020 8:17 pm

I attempted to read the full article here: https://journals.plos.org/plosgenetics/ ... en.1008612 but a lot of the science went over my head. Since you clearly have a better grasp of this, would you mind answering a question?

This is from the article:
"For Alzheimer’s disease, our estimate of the liability-scale SNP heritability for the full 2013 dataset [39] is 15% for prevalence of 14% for those aged 71 older, half from APOE, while the recent “M2” and “M3” models of Zhang et al [14] gave values of 7% and 10% respectively–see S1 Appendix (p. S13)."

Does this mean that they believe only about 15% of AD is from genes? And that only half of that is from APOE? Or am I completely misunderstanding this?

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floramaria
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Re: Genetic Architecture of AD: Update

Postby floramaria » Sat Oct 17, 2020 2:38 pm

J11 wrote:Great article! Will need to read the fine print, though, as they introduce a fair number of new concepts
to understand.

anotherdreamer wrote:I attempted to read the full article here: https://journals.plos.org/plosgenetics/ ... en.1008612 but a lot of the science went over my head. Since you clearly have a better grasp of this, would you mind answering a question?

This is from the article:
"For Alzheimer’s disease, our estimate of the liability-scale SNP heritability for the full 2013 dataset [39] is 15% for prevalence of 14% for those aged 71 older, half from APOE, while the recent “M2” and “M3” models of Zhang et al [14] gave values of 7% and 10% respectively–see S1 Appendix (p. S13)."

Does this mean that they believe only about 15% of AD is from genes? And that only half of that is from APOE? Or am I completely misunderstanding this?

I can't weigh in o this myself because I don't understand it. I am re-posting anotherdreamer's question while also quoting J11 , so J11 will be notified.
anotherdreamer, when you are hoping for a direct response from someone who post you are responding to it is helpful to use the quote function. You can find info on this and other helpful hints for navigating the website most effectively at How-To Get the Most out of the ApoE4.info website
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anotherdreamer
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Re: Genetic Architecture of AD: Update

Postby anotherdreamer » Sat Oct 17, 2020 6:09 pm

floramaria wrote:
J11 wrote:anotherdreamer, when you are hoping for a direct response from someone who post you are responding to it is helpful to use the quote function. You can find info on this and other helpful hints for navigating the website most effectively at How-To Get the Most out of the ApoE4.info website


Thank you, Floramaria! I didn't realize you had to be quoted to get an alert.

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floramaria
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Re: Genetic Architecture of AD: Update

Postby floramaria » Sat Oct 17, 2020 6:52 pm

anotherdreamer wrote:Thank you, Floramaria! I didn't realize you had to be quoted to get an alert.
You are welcome!
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