Astral Codex Ten Podcast feed 07月01日 08:55
Missing Heritability: Much More Than You Wanted To Know
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文章探讨了关于“缺失的遗传力”的争议。在20世纪中期,环境因素被认为是塑造个性的关键。然而,70年代的孪生子研究显示,基因对行为特征,尤其是智商(IQ)有显著影响。随着基因科学的发展,研究者开始寻找与教育程度(EA)相关的基因。虽然全基因组关联研究取得进展,但仍有大量遗传力未能通过基因解释,即“缺失的遗传力”。文章介绍了两种解释:孪生子研究可能存在偏差,或尚未发现所有相关基因。作者受到Sasha Gusev等人的启发,深入研究了这一争议,并探讨了相关研究的现状。

🧬 20世纪中期,主流观点认为后天环境,如父母、同伴和宣传,是塑造个性的主要因素。

🔬 70年代的孪生子研究颠覆了这一观点,表明基因对行为特征,尤其是智商(IQ)有重要影响,估算IQ的遗传力约为60%。

📚 随着基因科学发展,研究者开始关注教育程度(EA)与基因的关系。全基因组关联研究发现了与EA相关的基因,但仍有大量遗传力未能通过基因解释,即“缺失的遗传力”。

🤔 针对“缺失的遗传力”,存在两种主要假说:一是孪生子研究可能高估了遗传力;二是尚未发现所有与EA相关的基因。文章探讨了这两种假说的辩论和研究现状。

The 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

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遗传力 基因 教育程度 智商 全基因组关联研究
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