Missing Heritability: Much More Than You Wanted To Know
Release Date: 07/01/2025
Astral Codex Ten Podcast
I. Eliezer Yudkowsky’s is the original AI safety org. But the original isn’t always the best - how is Mesopotamia doing these days? As money, brainpower, and prestige pour into the field, MIRI remains what it always was - a group of loosely-organized weird people, one of whom cannot be convinced to stop wearing a in public. So when I was doing AI grantmaking last year, I asked them - why should I fund you instead of the guys with the army of bright-eyed Harvard grads, or the guys who just got Geoffrey Hinton as their celebrity spokesperson? What do you have that they don’t? MIRI...
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[I haven’t independently verified each link. On average, commenters will end up spotting evidence that around two or three of the links in each links post are wrong or misleading. I correct these as I see them, and will highlight important corrections later, but I can’t guarantee I will have caught them all by the time you read this.]
info_outlineAstral Codex Ten Podcast
[This is one of the finalists in the 2025 review contest, written by an ACX reader who will remain anonymous until after voting is done. I’ll be posting about one of these a week for several months. When you’ve read them all, I’ll ask you to vote for a favorite, so remember which ones you liked] If you’ve been following this blog for long, you probably know at least a bit about pharmaceutical research. You might know a bit about the sort of to influence doctors’ prescribing habits, or how it takes on average to bring a new medication to market, or something about the which...
info_outlineAstral Codex Ten Podcast
"You made him lower than the angels for a short time..." God: …and the math results we’re seeing are nothing short of incredible. This Terry Tao guy - Iblis: Let me stop you right there. I agree humans can, in controlled situations, provide correct answers to math problems. I deny that they truly understand math. I had a conversation with one of the humans recently, which I’ll bring up here for the viewers … give me one moment …
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You can sign the letter . The Trump administration has been , and people and groups with business before the administration have started laundering criticism through other sources with less need for goodwill. So I have been asked to share , which needs signatures from scientists, doctors, and healthcare professionals. The authors tell me (THIS IS NOT THE CONTENTS OF THE LETTER, IT’S THEIR EXPLANATION, TO ME, OF WHAT THE LETTER IS FOR): The NIH has spent at least than Congress has appropriated to them, which is bad because medical research is good and we want more of it. In May, that he...
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AI psychosis (, ) is an apparent phenomenon where people go crazy after talking to chatbots too much. There are some high-profile anecdotes, but still many unanswered questions. For example, how common is it really? Are the chatbots really driving people crazy, or just catching the attention of people who were crazy already? Isn’t psychosis supposed to be a biological disease? Wouldn’t that make chatbot-induced psychosis the same kind of category error as chatbot-induced diabetes? I don’t have all the answers, so think of this post as an exploration of possible analogies and precedents...
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Finalist #9 in the Review Contest [This is one of the finalists in the 2025 review contest, written by an ACX reader who will remain anonymous until after voting is done. I’ll be posting about one of these a week for several months. When you’ve read them all, I’ll ask you to vote for a favorite, so remember which ones you liked] Ollantay is a three-act play written in Quechua, an indigenous language of the South American Andes. It was first performed in Peru around 1775. Since the mid-1800s it’s been performed more often, and nowadays it’s pretty easy to find some company in Peru...
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[original post ] #1: Isn’t it possible that embryos are alive, or have personhood, or are moral patients? Most IVF involves getting many embryos, then throwing out the ones that the couple doesn’t need to implant. If destroying embryos were wrong, then IVF would be unethical - and embryo selection, which might encourage more people to do IVF, or to maximize the number of embryos they get from IVF, would be extra unethical. I think a default position would be that if you believe humans are more valuable than cows, and cows more valuable than bugs - presumably because humans are more...
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Finalist #8 in the Review Contest [This is one of the finalists in the 2025 review contest, written by an ACX reader who will remain anonymous until after voting is done. I’ll be posting about one of these a week for several months. When you’ve read them all, I’ll ask you to vote for a favorite, so remember which ones you liked] I. The Men Are Not Alright Sometimes I’m convinced there’s a note taped to my back that says, “PLEASE SPILL YOUR SOUL UPON THIS WOMAN.” I am not a therapist, nor in any way certified to deal with emotional distress, yet my presence seems to cause people...
info_outlineAstral Codex Ten Podcast
A guest post by David Schneider-Joseph The “amyloid hypothesis” says that Alzheimer’s is caused by accumulation of the peptide amyloid-β. It’s the leading model in academia, but a favorite target for science journalists, contrarian bloggers, and neuroscience public intellectuals, who point out problems like: Some of the research establishing amyloid's role turned out to be fraudulent. The level of amyloid in the brain doesn’t correlate very well with the level of cognitive impairment across Alzheimer’s patients. Several strains of mice that were genetically programmed to have...
info_outlineThe Story So Far
The mid-20th century was the golden age of nurture. Psychoanalysis, behaviorism, and the spirit of the ‘60s convinced most experts that parents, peers, and propaganda were the most important causes of adult personality.
Starting in the 1970s, the pendulum swung the other way. Twin studies shocked the world by demonstrating that most behavioral traits - especially socially relevant traits like IQ - were substantially genetic. Typical estimates for adult IQ found it was about 60% genetic, 40% unpredictable, and barely related at all to parenting or family environment.
By the early 2000s, genetic science reached a point where scientists could start pinpointing the particular genes behind any given trait. Early candidate gene studies, which hoped to find single genes with substantial contributions to IQ, depression, or crime, mostly failed. They were replaced with genome wide association studies, which accepted that most interesting traits were polygenic - controlled by hundreds or thousands of genes - and trawled the whole genome searching for variants that might explain 0.1% or even 0.01% of the pie. The goal shifted toward polygenic scores - algorithms that accepted thousands of genes as input and spit out predictions of IQ, heart disease risk, or some other outcome of interest.
The failed candidate gene studies had sample sizes in the three or four digits. The new genome-wide studies needed five or six digits to even get started. It was prohibitively difficult for individual studies to gather so many subjects, genotype them, and test them for the outcome of interest, so work shifted to big centralized genome repositories - most of all the UK Biobank - and easy-to-measure traits. Among the easiest of all was educational attainment (EA), ie how far someone had gotten in school. Were they a high school dropout? A PhD? Somewhere in between? This correlated with all the spicy outcomes of interest people wanted to debate - IQ, wealth, social class - while being objective and easy to ask about on a survey.
Twin studies suggested that IQ was about 60% genetic, and EA about 40%. This seemed to make sense at the time - how far someone gets in school depends partly on their intelligence, but partly on fuzzier social factors like class / culture / parenting. The first genome-wide studies and polygenic scores found enough genes to explain 2%pp1 of this 40% pie. The remaining 38%, which twin studies deemed genetic but where researchers couldn’t find the genes - became known as “the missing heritability” or “the heritability gap”.
Scientists came up with two hypothesis for the gap, which have been dueling ever since:
- Maybe twin studies are wrong.
- Maybe there are genes we haven’t found yet
For most of the 2010s, hypothesis 2 looked pretty good. Researchers gradually gathered bigger and bigger sample sizes, and found more and more of the missing heritability. A big 2018 study increased the predictive power of known genes from 2% to 10%. An even bigger 2022 study increased it to 14%, and current state of the art is around 17%. Seems like it was sample size after all! Once the samples get big enough we’ll reach 40% and finally close the gap, right?
This post is the story of how that didn’t happen, of the people trying to rehabilitate the twin-studies-are-wrong hypothesis, and of the current status of the debate. Its most important influence/foil is Sasha Gusev, whose blog The Infintesimal introduced me to the new anti-hereditarian movement and got me to research it further, but it’s also inspired by Eric Turkheimer, Alex Young (not himself an anti-hereditarian, but his research helped ignite interest in this area), and Awais Aftab.
(while I was working on this draft, the East Hunter Substack wrote a similar post. Theirs is good and I recommend it, but I think this one adds enough that I’m publishing anyway)
https://www.astralcodexten.com/p/missing-heritability-much-more-than