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Health

Common variant for "IQ gene"?

Gene ExpressionBy Razib KhanApril 16, 2012 8:11 AM

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A few people have forwarded me this paper, Identification of common variants associated with human hippocampal and intracranial volumes:

...Whereas many brain imaging phenotypes are highly heritable...identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10−16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10−12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10−7).

Look at the sample sizes. Beware of behavior genomics with small sample sizes. Paul Thompson, one of the many authors of this paper, is giving media interviews. To me that's a good sign, as he's a very smart guy. He has some confidence in this study. Here's the section which is resulting in the forwards:

... In addition, the C allele of rs10784502 is associated, on average, with 9,006.7 mm3 larger intracranial volume, or 0.58% of intracranial volume per risk allele and is weakly associated with increased general intelligence by approximately 1.29 IQ points per allele.

I'm a homozygote for the T allele for what it's worth. But that's not surprising. Look at the population distribution of the C allele from the HapMap:

hapmap.jpg

I think CD-CV is played out when it comes to IQ or height. Note that the gene in which this SNP is located, HMGA2, is also implicated in height variation. In fact, aside from pathological mutations, this locus may have the largest effect height and IQ polymorphisms in replicable studies (genetic and genomic, linkage and GWAS, IQ studies have a history of not being replicated, probably because of low power). Update: See Luke Justins' comment. My post above was rooted in a mild misipression due to read-post-and-dash. My bad. So we'll see if the 'endophenotype' pans out.

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