Genetic architecture of intelligence from SNP distance measures

From a presentation by Steve Hsu (pdf slides):

Quantitative traits: many alleles, each of small effect. GWAS discovery of individual loci is hard.

But, phenotype differences must be associated with LARGE number of genetic differences.

Investigate pairwise genetic distance as g score (or height) are varied. Extract underlying genetic architecture:
1. Distribution of associated alleles dominated by small MAF (Minor Allele Frequency)
2. More (−) than (+) minor alleles (MAF < 0.5)
3. Rough estimate of 10k causal alleles in total [. . .]

Select outlier groups H and L. Averaging over pairs eliminates fluctuations in distance which are uncorrelated to phenotype.

Average pairwise genetic distance changes with mean IQ and IQ difference: ∼ 39 SNPs per population SD [. . .]

Low IQ = more rare (−) variants. Larger genetic distances between individuals. Similar results for height. [. . .]

Geniuses and Giants: Fewer deleterious alleles.

(A) 39 SNPs per SD of IQ suggests roughly 10k causal variants.

(B) Exceptional cognitive ability = of order 100’s fewer rare (−) variants than an average person.

Apropos of the last post, here's Hsu's comment when linking to these slides:
In the context of human genetics, it's clear there's plenty of room at the top -- possibly as much as +30 SDs based on existing variance in the human population! (Compare to the result of selection in maize.)
Nor does Hsu shrink from the practical implications:

Imagine what a couple might pay to ensure that they get the best out of 10 or 50 possible offspring, optimizing over their choice of heritable attributes. Compare this with the cost of a Harvard education or K-12 private school tuition. The cost of an IVF cycle is down to a few thousand dollars and could go even lower.

Genetic prediction at high accuracy will probably be possible once of order millions of genotype-phenotype data pairs are available for analysis. I predict about 5-10 years. The advance in the Nature article makes me confident that the necessary reproductive technologies will also be available.

I hope that progressive governments will make this procedure free for everyone. The benefits from increased economic output, decreased welfare and criminality rates, etc. far outweigh the cost of what I have described above ( = few cycles of IVF + running my algorithms provided at dirt cheap licensing rates ;-) [. . .]

You can't use US numbers for real medical costs -- our system has huge distortions. Few $K is the cost in Taiwan or Korea and success rates are if anything higher there. That's not even factoring the economies of scale that would arise if a large fraction of couples wanted it.

Who says the US is the first market for this?

No doubt Hsu is correct that Asia is unlikely to hesitate in applying the lessons of quantitative genetics to humans -- regardless of what Alexis Madrigal-types would have for the US. The Chinese government funds the genetics of intelligence study Hsu is involved in. Also see Hsu's slides from a previous talk (pdf):


• Suppose that we can non- destructively sequence gametes (sperm and egg cells).

• We can imagine parents choosing which gametes to unite in order to constitute their offspring.

• In particular, they might choose to unite gametes bearing many g-enhancing alleles. [. . .]

“Suppose we knew, for instance, twenty [loci affecting] mental characters. These would combine in over a million [homozygous] mental types. In practice each of these would naturally occur rather less frequently than one in a billion, or in a country like England, about once in 20,000 generations.

“It will give some idea as to the excellence of the best of these types when we consider that the Englishmen from Shakespeare to Darwin ... have occurred within ten generations; the thought of a race of men combining the illustrious qualities of these giants, and breeding true to them, is almost too overwhelming ...

“... but such a race will inevitably arise in whatever country first sees the inheritance of mental characters elucidated.”— RONALD A. FISHER, “MENDELISM AND BIOMETRY”

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