Monday, May 22, 2017

NYTimes: In ‘Enormous Success,’ Scientists Tie 52 Genes to Human Intelligence

The Nature Genetics paper below made a big splash in today's NYTimes: In ‘Enormous Success,’ Scientists Tie 52 Genes to Human Intelligence. The picture above is of a UK Biobank storage facility for blood (DNA) samples.

The results are not especially surprising to people who have been following the subject, but this is the largest sample of genomes and cognitive scores yet analyzed (~80k individuals). SSGAC has assembled a much larger dataset (~750k, soon to be over 1M; over 600 genome-wide significant SNP hits), but are working with a proxy phenotype for cognitive ability: years of education.
Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

Nature Genetics (2017) doi:10.1038/ng.3869
Received 10 January 2017 Accepted 24 April 2017 Published online 22 May 2017

Intelligence is associated with important economic and health-related life outcomes1. Despite intelligence having substantial heritability2 (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered3, 4, 5. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10−8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10−6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10−6). Despite the well-known difference in twin-based heratiblity2 for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10−29). These findings provide new insight into the genetic architecture of intelligence.
Perhaps the most interesting aspect of this study is the further evidence it provides that many (the vast majority?) of the hits discovered by SSGAC are indeed correlated with cognitive ability (as opposed to other traits such as Conscientiousness, which might influence educational attainment without affecting intelligence):
To examine the robustness of the 336 SNPs and 47 genes that reached genome-wide significance in the primary analyses, we sought replication. Because there are no reasonably large GWAS for intelligence available and given the high genetic correlation with educational attainment, which has been used previously as a proxy for intelligence7, we used the summary statistics from the latest GWAS for educational attainment21 for proxy-replication (Online Methods). We first deleted overlapping samples, resulting in a sample of 196,931 individuals for educational attainment. Of the 336 top SNPs for intelligence, 306 were available for look-up in educational attainment, including 16 of the independent lead SNPs. We found that the effects of 305 of the 306 available SNPs in educational attainment were sign concordant between educational attainment and intelligence, as were the effects of all 16 independent lead SNPs (exact binomial P < 10−16; Supplementary Table 14). ...
Carl Zimmer did a good job with the Times story. The basic ideas, that
0. Intelligence is (at least crudely) measurable
1. Intelligence is highly heritable (much of the variance is determined by DNA)
2. Intelligence is highly polygenic (controlled by many genetic variants, each of small effect)
3. Intelligence is going to be deciphered at the molecular level, in the near future, by genomic studies with very large sample size 
are now supported by overwhelming scientific evidence. Nevertheless, they are and have been heavily contested by anti-Science ideologues.

For further discussion of points (0-3), see my article On the genetic architecture of intelligence and other quantitative traits.

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