Linking genes, brain structure and intelligence.
(Gray & Thompson 2004)

a | Genetic influences on intelligence have been assessed directly (top arrow). The consensus of many studies is that at least 40% of the variability in general cognitive ability ("Spearman's g factor") can be attributed to genetic factors. Gene effects on brain structure can be assessed by collecting MRI (Magnetic Resonance Imaging) brain scans (left) from twins or extended families, and comparing volumes of grey matter (green), white matter (red) or cerebrospinal fluid (blue). Overall brain
volume is 85% heritable and correlates with psychometric intelligence (0.33)*. Genetic modelling has shown that g and grey matter volumes depend on the same set of genes (the genetic correlation is about 0.25)*. The volume of grey matter in each lobe is genetically influenced to different degrees (the volume of grey matter in the frontal lobe, shown at right in yellow and pink, is highly heritable).

b | Genetic influences on brain structure can be assessed using statistical maps. In the classical twin design, a feature is heritable if within-pair correlations (typically called intra-class correlations) are higher for pairs of identical twins (who share all their genes, except for rare somatic mutations) and lower for same-sex fraternal twin pairs (who, on average, share half their genes). To better understand genetic influences on brain structure, correlations are shown for regional grey matter volumes in sets of identical (monozygotic (MZ)) and fraternal (dizygotic (DZ)) twins. These correlations vary across the brain surface (red, highly correlated; blue, less well correlated). The structure of the brains of identical twins is more similar than that of fraternal twins. F, frontal cortex; S/M, primary sensorimotor cortex; W, Wernicke’s area.

c | Heritability
(h2) is defined as the fraction of the phenotypic variance due to genotypic variance (as compared with environmental variance). Because monozygotic (MZ) and dizygotic (DZ) twins are related by 1.0 and 0.5, respectively, heritability for a trait value (x) can be estimated as twice the difference between the correlations measured in monozygotic versus dizygotic twins:  h2(x) = (2)(rMZ(x) - rDZ(x)) .  This applies for example to measures of grey matter volumes at each location in the cortex.

d | Statistical significance of the heritabilities. These can also be estimated from path analyses. Variations in grey matter volumes are strongly influenced by genetic factors, especially in frontal brain regions (for example, the dorso-lateral pre-frontal cortex). A subsequent study in a larger, independent sample found that variations in total grey matter volume were almost entirely attributable to genetic factors (but three-dimensional maps of these effects were not created). These genetically mediated differences in brain structure explain a proportion of the variation in general cognitive ability. This ability is also influenced by non-genetic factors such as education and nutrition, prenatal and family environments, training and environmental hazards such as lead poisoning.

*Note that "statistical significance" means that the degree of correlation is non-random, not that the value of the correlation is large. In part (a), the genetic correlation of Spearman's g with brain metrics are significant (non-random) but small (0.25 & 0.33). In general, studies with more data are able to identify statistical significance of smaller phenotypic differences. ]

Figure 3 from Gray & Thompson 2004. Nature Reviews Neuroscience 5, 471-482 (2004)
Emphasis added; text slightly (a,b,d) or extensively (c) edited
2012 Steven M. Carr