Most Reported Genetic Associations With Intelligence Are Likely False Positives

Another current article,

Epigenesis for epidemiologists: does evo-devo have implications for population health research and practice? George Davey Smith Int. J. Epidemiol. (2012) 41 (1): 236-247.

doi: 10.1093/ije/dys016

sums up the most up-to-date research similarly. The author mentions an earlier author who predicted this outcome in 1927.

"Pearl's prediction (based on biological reasoning) has proved spectacularly prescient: molecular genetics suggests that of Mendelian influences of individually tiny effect contribute to the heritability of intelligence. . . . Indeed, the shuffling of such tiny Mendelian effects could, Pearl said, 'be relied on, I think, to produce in the future, as it has in the past, Shakespeares, Lincolns, and Pasteurs, from socially and economically humble origins.'" (citing Pearl, R. Differential Fertility. Q. Rev. Biol. 1927;2:102-18).

I've had the privilege of meeting Wendy Johnson, a human intelligence researcher who has an undergraduate degree in mathematics and who has worked with both the twin studies researchers at Minnesota and with Ian Deary at Edinborough. Her review articles are very informative on the latest directions in studies of genetic influences on human intelligence.

The review article "The neuroscience of human intelligence differences" by Deary and Johnson and Penke (2010) relates specifically to human intelligence:

http://www.larspenke.eu/pdfs/Deary_Penke_Johnson_2010_-_Neur...

"At this point, it seems unlikely that single genetic loci have major effects on normal-range intelligence. For example, a modestly sized genome-wide study of the general intelligence factor derived from ten separate test scores in the cAnTAB cognitive test battery did not find any important genome-wide single nucleotide polymorphisms or copy number variants, and did not replicate genetic variants that had previously been associated with cognitive ability[note 48]."

The review article Johnson, W. (2010). Understanding the Genetics of Intelligence: Can Height Help? Can Corn Oil?. Current Directions in Psychological Science, 19(3), 177-182

http://apsychoserver.psych.arizona.edu/JJBAReprints/PSYC621/...

looks at some famous genetic experiments to show how little is explained by gene frequencies even in thoroughly studied populations defined by artificial selection.

"Together, however, the developmental natures of GCA and height, the likely influences of gene–environment correlations and interactions on their developmental processes, and the potential for genetic background and environmental circumstances to release previously unexpressed genetic variation suggest that very different combinations of genes may produce identical IQs or heights or levels of any other psychological trait. And the same genes may produce very different IQs and heights against different genetic backgrounds and in different environmental circumstances."

> "All of our analyses controlled for graduate/sibling status, age, gender, and the interactions of these variables, as well as the first three principal components of the genetic data from the full set of 90 genotyped SNPs (to account for possible population stratification)."

It is customary to do genomic control using likely-uncorrelated SNPs (i.e., excluding the 13 SNPs nominally reported to be in LD with the trait of interest). That they included these 13 when estimating pop strat from a small overall number of alleles makes me concerned that they may have unintentionally "controlled for" the actual effect, if any did exist.

Even then, since they controlled for the first 3 PCs of that data, and I would assume the 13 candidate SNPs to be in linkage equilibrium, they shouldn't be getting rid of more than a couple actual associations, yet they find none replicate. So my observation is probably just a curio.

Very interesting. Though I'm not finding it overly surprising based on everything I've read on effects of environment and nurture on growth and potential.

Few snippets I found interesting:

"These and our other results, together with the failure to date of whole-genome association studies to find genes associated with g, are consistent with the view that g is a highly polygenic trait on which common genetic variants individually have only small effects."

"By far the most plausible explanation for failures to replicate reported SNP-g (single-nucleotide polymorphisms) associations in our three studies, however, is that the original studies whose findings we sought to replicate did not have sufficient sample sizes—and not because of any error in design or execution."

"Our results add IQ to the list of phenotypes that must be approached with great caution when considering published molecular genetic associations... Failing to exercise such caution may hamper scientific progress by allowing for the proliferation of potentially false results, which may then influence the research agendas of scientists who do not realize that the associations they take as a starting point for their efforts may not be real... And the dissemination of false results to the public may lead to incorrect perceptions about the state of knowledge in the field, especially knowledge concerning genetic variants that have been described as “genes for” traits on the basis of unintentionally inflated estimates of effect size and statistical significance."

...bracing for the inevitable headlines that claim exactly the opposite of the first sentence of the abstract: "General intelligence (g) and virtually all other behavioral traits are heritable."

Just to be clear, this doesn't disprove that intelligence is an inheritable trait; merely that there is so far no clear candidates "an intelligence gene" and there may never be such.