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, 23 (11), 1314-23

Most Reported Genetic Associations With General Intelligence Are Probably False Positives

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Most Reported Genetic Associations With General Intelligence Are Probably False Positives

Christopher F Chabris et al. Psychol Sci.

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 g and 12 specific genetic variants (in the genes DTNBP1, CTSD, DRD2, ANKK1, CHRM2, SSADH, COMT, BDNF, CHRNA4, DISC1, APOE, and SNAP25) using data sets from three independent, well-characterized longitudinal studies with samples of 5,571, 1,759, and 2,441 individuals. Of 32 independent tests across all three data sets, only 1 was nominally significant. By contrast, power analyses showed that we should have expected 10 to 15 significant associations, given reasonable assumptions for genotype effect sizes. For positive controls, we confirmed accepted genetic associations for Alzheimer's disease and body mass index, and we used SNP-based calculations of genetic relatedness to replicate previous estimates that about half of the variance in g is accounted for by common genetic variation among individuals. We conclude that the molecular genetics of psychology and social science requires approaches that go beyond the examination of candidate genes.

Figures

Figure 1
Figure 1
Statistical power of Studies 1–3 to detect significant associations between SNPs and g, plotted as a function of the percentage of variance in g explained by the SNP (or genotype in the case of APOE e4). Note that the x-axis runs from 0% to 1% out of a total of 100% variance in g, so that 0.1 corresponds to 1/1000 of the total trait variance. Power was estimated for the three studies using the full sample size (“Upper” bound on power for WLS, STR, and FHS) and using the number of unrelated individuals only (“Lower” bound on power for WLS, STR, and FHS), yielding six power curves. Calculations were performed using the tool created by Purcell, Cherny, and Sham (2003) [pngu.mgh.harvard.edu/~purcell/gpc/qtlassoc.html]. Assuming an effect size of 0.1% of variance for each genotype tested (shown by the dashed line), we should have observed between 10.6 and 14.7 significant associations (for the unrelated and full samples, respectively), but we only observed 1.
Figure 2
Figure 2
Regression coefficients for each genotype (i.e., difference in number of IQ points associated with each copy of the minor allele), pooled across Studies 1–3. To minimize the variance of the estimator, pooling was done by weighting the three estimated regression coefficients for each SNP by the inverse of their estimated variances, with the weights then normalized so that they sum to one. Error bars show 95% confidence intervals. For APOE, the bar shows the number of IQ points associated with possessing at least one e4 allele.

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