Shared genetic influences on adolescent body mass index and brain structure: A voxel-based morphometry study in twins

Abstract

Background: Previous research has demonstrated significant relationships between obesity and brain structure. Both phenotypes are heritable, but it is not known whether they are influenced by common genetic factors. We investigated the genetic etiology of the relationship between individual variability in brain morphology and BMIz using structural MRI in adolescent twins.

Method: The sample (n = 258) consisted of 54 monozygotic and 75 dizygotic twin pairs (mean(SD) age = 13.61(0.505), BMIz = 0.608(1.013). Brain structure (volume and density of gray and white matter) was assessed using VBM. Significant voxelwise heritability of brain structure was established using the Accelerated Permutation inference for ACE models (APACE) program, with structural heritability varying from 15 to 97%, depending on region. Bivariate heritability analyses were carried out comparing additive genetic and unique environment models with and without shared genetics on BMIz and the voxels showing significant heritability in the APACE analyses.

Results: BMIz was positively related to gray matter volume in the brainstem and thalamus and negatively related to gray matter volume in the bilateral uncus and medial orbitofrontal cortex, gray matter density in the cerebellum, prefrontal lobe, temporal lobe, and limbic system, and white matter density in the brainstem. Bivariate heritability analyses showed that BMIz and brain structure share ∼1/3 of their genes and that ∼95% of the phenotypic correlation between BMIz and brain structure is due to shared additive genetic influences. These regions included areas related to decision-making, motivation, liking vs. wanting, taste, interoception, reward processing/learning, caloric evaluation, and inhibition.

Conclusion: These results suggested genetic factors are responsible for the relationship between BMIz and heritable BMIz related brain structure in areas related to eating behavior.

Keywords: Adolescence; Density; Heritability; Obesity; VBM; Volume.

Figure 1:

Bivariate additive genetic non-shared environment heritability model. MZ = monozygotic, DZ = Dizygotic. A/E11/22 = Unique genetics/non-shared environment on BMIz/VBM. A/E21 = Shared genetics/non-shared environment between BMIz and VBM.

Figure 2:

Brain regions significantly related with BMIz. A: Gray and white matter density. B: Gray matter volume. Color scales indicate the significance size of the correlations. Yellow-red indicates significant positive correlations, whereas light blue to dark blue indicate negative correlations. Lighter colors indicate higher significance level (lower p-value).

Figure 3:

Voxelwise heritability of brain structure related to BMIz. Color scales indicate the proportion of phenotypic variance attributable to genetic factors. The yellow-red scale indicates heritability of density, and the blue scale indicates heritability of volume. Lighter colors represent higher heritability.

Figure 4:

Genetic correlations between BMIz and brain structure. A: Gray and white matter density. B: Gray matter volume. Yellow-red = positive correlations, light blue-blue = negative correlations.

Figure 5:

Literature-based eating and obesity related functions of regions phenotypically and genetically linked to BMIz in these analyses. Significant volume and density clusters in a glass brain color coded by relevant function. Striped clusters associated with multiple relevant functions, colors in striped clusters refer to cluster as a whole, not specific colored region. Black clusters (pulvinar, inferior temporal) have no known functional relevance.