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Mind

Most Reported Genetic Associations with General Intelligence Are Probably False Positives

Gene ExpressionBy Razib KhanDecember 12, 2011 3:49 AM

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The title says it all, and I yanked it from a paper that is now online (and free). It's of interest because of its relevance to the future genetic understanding of complex cognitive and behavioral traits. Here's the abstract:

General intelligence (g) and virtually all other behavioral traits are heritable. Associations between g and specific single-nucleotide polymorphisms (SNPs) in several candidate genes involved in brain function have been reported. We sought to replicate published associations between 12 specific genetic variants and g using three independent, well-characterized, longitudinal datasets of 5571, 1759, and 2441 individuals. Of 32 independent tests across all three datasets, only one was nominally significant at the p ~ .05 level. By contrast, power analyses showed that we should have expected 10–15 significant associations, given reasonable assumptions for genotype effect sizes. As positive controls, we confirmed accepted genetic associations for Alzheimer disease and body mass index, and we used SNP-based relatedness calculations to replicate estimates that about half of the variance in g is accounted for by common genetic variation among individuals. We conclude that different approaches than candidate genes are needed in the molecular genetics of psychology and social science.

My hunch is that these results will be unsatisfying to many people. The authors confirm and reassert the heritability of general intelligence, both by reiterating classical results, and utilizing novel genomic techniques. But, they also suggest that the candidate gene literature is nearly worthless because of the lack of power of most of the earlier studies. The latter is probably due to the genetic architecture of the trait. Intelligence may be determined by numerous genes of very small effect (e.g., 0.01% of the variance effected by one particular SNP), or, "rare, perhaps structural, genetic variants with modest to large effect sizes." The former case is pretty obvious, but what about the latter? I'm mildly skeptical of this because I'm curious why modest-to-large effect variants didn't show up in family-based studies (presumably within the family the same variants would localize to sections of the genetic map)? But I'm not fluent enough in the literature to know if there was a lot of work in this area with families previously. Related: Here's the first author's article in Commentary from the late 1990s, IQ Since "The Bell Curve".

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