Article Figures & Data
Figures
- Figure 1.
Genetically influenced focal GM density brain areas. Heritability estimates of GM density in focal brain areas in healthy adult humans are shown for the significance level thresholded A-map superimposed on axial and sagittal sections through the magnetic resonance image of the standardized reference brain (left) and for the complete A-map (right). The significance level thresholded A-map shows the voxels that had a significant fit of the genetic model compared with the other models based on the likelihood ratio test and using structural equation modeling. Moreover the level of significance was set at χ2 > 25.3 for Δdf = 1 and χ2 > 29.3 for Δdf = 2 after correction for multiple comparisons according to random field theory (the uncorrected significance levels would have been χ2 > 3.8 and χ2 > 6.0). Analyses were controlled for age, sex, and handedness. a, Left occipital cortex. b, Right medial frontal gyrus. c, Left and right Heschl's gyrus. d, Left amygdala and right parahippocampal gyrus. R, Right.
- Figure 2.
Genetically influenced focal WM density brain areas superimposed on the histologically defined map of the superior occipitofrontal fascicle. Heritability of WM density in focal brain areas in healthy adult humans is shown for the significance level thresholded A-map superimposed on axial and sagittal sections in the left (L) and right (R) hemisphere through the magnetic resonance image of the standardized reference brain (left) and superimposed on the histologically defined map of the occipitofrontal superior fascicle (middle) (reproduced with the permission of K.Z, K.A., and U.B.). The complete A-maps are shown on the right. Note that several of the genetically influenced focal WM density voxels shown on the left also overlapped with the histologically defined maps of the corpus callosum, optic radiation, and corticospinal tract, which are not shown in the middle figures because relatively few voxels overlapped with these white matter tracts. a, Axial section. b, c, Sagittal sections.
- Figure 3.
3D representation of genetically influenced focal WM density brain areas superimposed on the histologically defined map of the superior occipitofrontal fascicle. Three-dimensional glass brain representations (top left, left side view; top right, right side view; bottom left, superior view; bottom right, posterior view) of the variance in WM density found to be significantly influenced by genetic factors in healthy adult humans (orange) with the histologically defined map of the occipitofrontal superior fascicle (green) and lateral and third ventricles (blue). See also supplemental movie 1, available at www.jneurosci.org as supplemental material.
- Figure 4.
GM density in the right medial frontal cortex (top) and WM density in the left superior occipitofrontal fascicle (bottom). Dots represent values of GM and WM density (varying between 0 and 1) for individual MZ (left) and DZ (right) twin pairs at (x, y, z) (39, 43, 37) (top) and at (−17, 10, 25) (bottom). Twin 1 and twin 2 represent the two individuals of a twin pair. The correlation within MZ twin pairs is much higher than that in DZ twin pairs, indicating that the individual variation in GM and WM density in these areas is primarily determined by genes.
- Figure 5.
Cross-trait/cross-twin correlations for GM and WM density and VIQ/PIQ in MZ and DZ twin pairs ranging from 0 to 0.5. The cross-trait/cross-twin correlations were significant for GM density with VIQ in the right parahippocampal gyrus and for WM density with PIQ in the right superior occipitofrontal fascicle. A significant cross-trait/cross-twin correlation indicates that the genes influencing GM and WM density partly overlap with the genes that influence VIQ/PIQ. Note that, for illustration purposes, positive cross-correlations as shown here were not thresholded for significance. By definition, the cross-correlations in voxels that were not significantly determined by genetic factors could not become significant (because both factors, i.e., GM and WM density and VIQ and PIQ measures, have to be determined by genes to allow for inferences that possible mutual genes determine that association). Negative cross-correlations (data not shown) were present, but none of these reached significance. For details on these and other significant cross-trait/cross-twin correlations in the sample, see Table 3. Rt, Right.
Tables
MZ DZ SIB n individuals (MRI/IQ) 49/213 65/285 34/190 Sex, M/F (MRI) 34/15 33/32 19/15 Sex, M/F (IQ) 98/115 117/168 91/99 Hand, R/L, A (MRI) 41/8 54/11 29/5 Hand, R/L, A (IQ) 183/30 251/34 175/15 Age, years (MRI) 28.3 (3.6) 29.2 (8.7) 29.6 (4.8) Age, years (VIQ, PIQ) 37.7 (36.6) 36.6 (13.3) 36.7 (13.2) VIQ (% correct) 63.3 (13.3) 64.9 (12.2) 65.4 (13.3) PIQ (% correct) 76.0 (12.8) 75.0 (14.0) 75.6 (13.2) -
Values are shown as mean (SD). M, Male; F, female; R, right; L, left; A, ambidexter; SIB, singleton siblings of twin pairs.
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- Table 2.
Heritability estimates for focal gray and white matter areas with significant genetic contribution
Left hemisphere Right hemisphere Talairacha Heritability Talairach Heritability x y z x y z Gray matter Superior frontal −5 58 35 0.76 Superior frontalb 7 43 51 0.80 Medial frontal −37 34 39 0.78 Superior frontal 21 53 33 0.76 Postcentral gyrus −55 −29 57 0.83 Medial frontalb 29 43 37 0.82 Posterior cingulate −5 −33 23 0.83 Medial frontal 43 22 43 0.83 Heschl's gyrus −27 −31 21 0.80 Heschl's gyrus 37 −36 19 0.77 Amygdala −29 −5 −7 0.80 Amygdala 21 −5 −15 0.55 Occipital cortex −25 −60 11 0.85 Parahippocampal 25 −31 −11 0.69 White matter Superior occipitofrontal fascicle −17 10 25 0.79 Superior occipitofrontal fascicle 23 22 15 0.77 Corpus callosum −21 −9 35 0.82 Corpus callosum 3 19 17 0.80 Optic radiation −35 −48 17 0.69 Optic radiation 37 −36 17 0.79 Corticospinal tract −17 −12 21 0.78 Corticospinal tract 21 −16 37 0.79 -
↵aThe x values indicate the distance in millimeters from the left (negative values) to the right (positive values) side of the brain passing through the anterior commissure. The y values indicate the distance from posterior (negative values) to anterior (positive values). The z values indicate the distance from inferior (negative values) to superior (positive values).
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↵bTwo separate genetically determined areas were identified within the superior and medial frontal cortices.
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- Table 3.
Observed (phenotypic) correlations, cross-trait/cross-twin correlations, and genetic correlations
Left hemisphere, IQ (x, y, z) Correlation Right hemisphere, IQ (x, y, z) Correlation Observed (rp) Cross-trait/cross-twin Genetic (rg) Observed (rp) Cross-trait/cross-twin Genetic (rg) MZ DZ MZ DZ Gray matter Gray matter Occipital cortex, PIQ (−21, −62, 13) 0.17 0.08 −0.06 0.23 Medial frontal, PIQ (41, 22, 43) 0.25 0.32 0.02 0.37 White matter Parahippocampal, PIQ (23, −36, −9) 0.23 0.24 −0.04 0.40 Superior occipitofrontal fascicle, PIQ (−21, −24, 35) 0.17 0.18 0.04 0.24 Parahippocampal, VIQ (23, −38, −7) 0.11 0.15 −0.02 0.19 Corpus callosum, PIQ (−15, 3, 33) 0.18 0.17 0.17 0.22 White matter Optic radiation, PIQ (−35, −48, 17) 0.26 0.28 0.01 0.39 Superior occipitofrontal fascicle, PIQ (21, −29, 31) 0.35 0.25 0.08 0.32 Corpus callosum, VIQ (15, 3, 37) 0.14 0.13 0.02 0.15 -
The observed correlation (rp) reflects the correlation that is found between GM and WM density and VIQ/PIQ within individuals. The cross-trait/cross-twin correlations show the correlations of focal GM and WM densities of a twin with the intelligence quotient of his/her cotwin and vice versa for MZ and DZ twins (or sibling pairs) separately. If the correlation between GM and WM density of a twin and VIQ or PIQ in the cotwin is larger in MZ than in DZ twins, this indicates that the genes influencing GM and WM density partly overlap with the genes that influence VIQ/PIQ. The extent of the overlap is reflected by the magnitude of the genetic correlation (rg). rg reflects the correlation between the set of genes that influences focal GM and WM density and the set of genes that influences VIQ/PIQ. rp = rgh1h2 + ree1e2 (i.e., the phenotypic correlation is rg weighted by the square roots of the heritabilities h1 for GM and WM density and h2 for VIQ/PIQ plus the unique environmental component ree1e2).
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Supplemental data
Files in this Data Supplement:
- supplemental material - Movie of 3D glass brain representation of genetically influenced focal WM density brain areas superimposed on the histologically defined map of the superior occipitofrontal fascicle. Shown are the variance in WM density found to be significantly influenced by genetic factors in healthy adult humans (orange), the histologically defined map of the occipitofrontal superior fascicle (green), and the lateral and third ventricles (blue).
