I believe down syndrome is caused by a chromosome disorder, which is covered in the blog post. Risk does indeed rise sharply with maternal age past ~35.
garymm
Karma: 46
I just spoke to someone at Orchid who says their basic pricing is $2,500 per embyro for their most thorough testing, but they do have some sort of volume discount. They didn’t tell me when the discount kicks in.
Not sure if you saw the full post at the link, but some absolute risks, such as for miscarriage, are much higher. And for me personally a 1% risk of having a child with a serious mental disability is really scary. Perhaps not for you.
The dangers of reproducing while old
Specifically, after self-supervised pretraining, an LLM outputs exactly the thing that it expects to see. (After RLHF, that is no longer strictly true, but RLHF is just a fine-tuning step, most of the behavioral inclinations are coming from pretraining IMO.)
Qualitatively the differences between a purely predictively-trained LLM and one after RLHF seems quite large (e.g., see the comparison between GPT-3 and InstructGPT examples from OpenAI).
I have a friend who’s a geneticist and is much more pessimistic about the expected impact of embryo selection on a given desired trait. I chatted with him and read some papers he suggested and I now have a lower estimate of the expected value of embryo selection than before.
Very curious to hear from other experts in this field who disagree, especially those who don’t have a financial conflict of interest!
It seems it’s quite unclear how to even measure how heritable a given trait is, with different methods giving wildly different answers. And even if a trait is highly heritable:
The variation between siblings (or rather embryos from the same parents) is likely to be quite a lot lower than the variation seen in the general population.
The variation that’s due to very rare genetic variants is likely not captured in today’s polygenic risk scores.
Some relevant papers, which I don’t claim to fully understand, but from which I’ve extracted the above as “the gist”:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130754/
Key thing there is probably table 2, which shows different estimates of heritability from different methods.
https://pubmed.ncbi.nlm.nih.gov/32997097/
Key quote:
“Therefore, the so-called SNV-based heritability gives the upper limit of the variance between people in their liability to a disease that can be explained by PRS and represents the variance explained by common DNA variants. As GWAS sample sizes increase, the variance explained by PRS will also increase and approach the SNV-based heritability. The SNV-based heritability estimates vary across diseases, but an approximate upper limit is approximately 30%. Although in principle, use of whole-genome sequence data could increase the variance explained by PRS (because more variance would be tagged by measured markers, ie, the SNV-based heritability approaches the heritability), it is unlikely (at least in the short term) to improve PRS (eAppendix in the Supplement). Risk stratification based on current and future PRS is illustrated in Figure 4.”
The supplement is mostly a verbal argument along the lines of “there are just huge number of rare variants, each of which exists in only a few people, so it will be difficult to figure out how to use them to improve phenotype prediction.”
Thanks for this awesome post. Biggest update for me is “there might be a way to get screening for traits not advertised by Genomic Prediction”, but I still have no idea of the cost or the probability of success :-) Would be great to hear from people who have more info on this.
I recently weighed the pros and cons of IVF vs old-fashioned conception and went old-fashioned because:
1. This article claims “different embryo culture media give rise to different birthweights and growth patterns in children” and “children born after ART have altered epigenetic profiles”. I’m not an expert but I read it and found it quite plausible that there are ways that IVF can cause worse health outcomes. Very hard to tell without randomized trials, and all trials on IVF vs non-IVF are going to be heavily confounded.2. My child would be only 1⁄4 European ancestry and as you note the current predictors perform worse on non-Europeans. If we had good predictors for my child’s ancestry mix, then I’d probably go with IVF despite the possible downsides I noted above. Hopefully the new bio-banks you cited will enable that soon.
This article claims “different embryo culture media give rise to different birthweights and growth patterns in children” and “children born after ART have altered epigenetic profiles”.
I’m not an expert but I read it and found it quite plausible that there are ways that IVF can cause worse health outcomes. Would love to read a thorough critique of it!
Posting this here since I found it useful.
I think the really worth-while stuff is in the section “When Is Parenthood Associated With Well-Being?
Exploring Moderators” which starts on page 33.
Posting this here since I found it useful.
I think the really worth-while stuff is in the section “When Is Parenthood Associated With Well-Being?
Exploring Moderators” which starts on page 33.
Note: Alcor is no longer accepting new associate members (according to the page linked to in OP).
For people over 18 years old, membership dues are currently $15 x (age at time of sign up).
Would be great if you could update the post so it stays up-to-date.
Thanks for writing this!
I just contacted Alcor about paying with a trust and they wrote back “Alcor does not accept Cryopreservation Funding Trusts at this time.”
It seems like life insurance and prepayment are the only options.
Has anyone found good data or have an informed guesstimate on what fraction of kids who are non-verbal or minimally verbal at age X, will become verbal by age Y?
I found this old (1987) study by D. Bishop, and A. Edmundson which says:
“87 language-impaired children were assessed at the ages of 4, 4 1⁄2, and 5 1⁄2 years on a battery of language measures. In 37% of children, who were termed the “good outcome group,” the language disorder had resolved by the age of 5 1⁄2 years so that children were indistinguishable from a control group. “
There’s probably something more recent / or better. Thanks!