Nature Molecular Psychiatry (29 January 2013) | doi:10.1038/mp.2012.184
Childhood intelligence is heritable, highly polygenic and associated with FNBP1L
Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6–18 years) from 17 989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22–46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10−15, 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10−5), 3.5% (P=10−3) and 0.5% (P=6 × 10−5) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.
Compare to this figure for height and BMI from an earlier post: Five years of GWAS discovery. It appears we may be close to the threshold required to find the first genome-wide significant hits.
7 comments:
I already found the abstract, and it was interesting that the most significant SNP that 2011 Deary study was also significant here.
BTW, since I only saw the abstract, tell us what are SNPs are highly significant.
Paper link: http://www.genepi.qimr.edu.au/contents/p/staff/BENYAMIN_CHICPaperEPUB.pdf
Steve, did this paper cast any light on the characteristics of deleterious variants you discuss in http://infoproc.blogspot.com/2012/10/deleterious-variants-affecting-traits.html ? This seems relevant, but I'm not sure how to interpret: "Since the estimates of total additive genetic variation from common SNPs are a lower limit of narrow-sense heritability, these results imply that there are many common causal variants with small effects segregating in the population, because rare variants are not in sufficient linkage disequilibrium with the genotyped and imputed SNPs to be captured by our whole-genome method."
Can you give any news on the status of the BGI study? Any idea when sequencing results will be available?
If I read that right it may push the cost of engineering our way out of stupidity up.
I was hoping for one or two mutations that count, although I think possibly the analysis methods used might not be good for spotting those sorts (if they exist).
We are getting sequences back right now. But there was a problem with DNA extraction from a subset of samples, which caused a delay. If you are in the study you will be getting an email soon with more details.
One interpretation of the Visscher-type estimate of heritability is that it is common variants causing the phenotype variation. Statements to this effect often appear in his papers; the logic is that low frequency variants are only in weak LD with common SNPs, so they can't account for the observed phenotype-relatedness correlation.
Another interpretation (not completely ruled out, AFAIK) is that relatedness as measured using SNPs is correlated with the presence of deleterious variants: two individuals who have higher SNP relatedness are also more likely to be similar in their level of deleterious rare variants. That might account for the measured heritability even if the actual causal variants are not directly detected by the SNP chips. Time will tell.
Is the difference in heritability estimates .22 to .46 significant. One was only for Avon county and another only for Minnesota. The .22 is for England and Wales (TEDS). Could this lower figure be explained by the wider range of environments in the TEDS population?
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I don't see why relatedness as measured using SNPs couldn't be correlated with any type of variant not measured by GWAS. Tielbeek et al is a GWAS that found a high heritability estimate (55%) for antisocial personality disorder, which is high enough to suggest a "crowding out" of potential heritability ascribed to candidate VNTRs, like those of MAOA and DRD4. Chabris et al went so far as to call for journals to stop publishing candidate gene research. However, as I look through the MAOA literature, I am not finding a decline effect. Instead, I am finding a sort of reverse-engineering of the alleles' effects (on enzyme levels, fMRI enzyme activity, metabolytes) that gives me more confidence in the candidate research.
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