Heritability of volumetric brain changes and height in children entering puberty

Abstract

The human brain undergoes structural changes in children entering puberty, while simultaneously children increase in height. It is not known if brain changes are under genetic control, and whether they are related to genetic factors influencing the amount of overall increase in height. Twins underwent magnetic resonance imaging brain scans at age 9 (N = 190) and 12 (N = 125). High heritability estimates were found at both ages for height and brain volumes (49-96%), and high genetic correlation between ages were observed (r(g) > 0.89). With increasing age, whole brain (+1.1%), cerebellum (+4.2%), cerebral white matter (+5.1%), and lateral ventricle (+9.4%) volumes increased, and third ventricle (-4.0%) and cerebral gray matter (-1.6%) volumes decreased. Children increased on average 13.8 cm in height (9.9%). Genetic influences on individual difference in volumetric brain and height changes were estimated, both within and across traits. The same genetic factors influenced both cerebral (20% heritable) and cerebellar volumetric changes (45%). Thus, the extent to which changes in cerebral and cerebellar volumes are heritable in children entering puberty are due to the same genes that influence change in both structures. The increase in height was heritable (73%), and not associated with cerebral volumetric change, but positively associated with cerebellar volume change (r(p) = 0.24). This association was explained by a genetic correlation (r(g) = 0.48) between height and cerebellar change. Brain and body each expand at their own pace and through separate genetic pathways. There are distinct genetic processes acting on structural brain development, which cannot be explained by genetic increase in height.

Figure 1

Path diagram representing the longitudinal genetic model fitted to the data collected at age 9 and 12 years. Squares represent the observed phenotype of interest (e.g., height or brain volumes) in twin 1 and twin 2, and the circles represent latent, unobserved factors. A1, C1, and E1 influence the phenotype at age 9 and 12 years; A2, C2, and E2 influence the phenotype at age 12, but not at age of 9 years. Double headed arrows represent correlations between the genotypes of twins (1.0 for MZ and 0.5 for DZ pairs). The influence of the first set of latent factors on the phenotype at age 9 is represented by factor loadings (one headed arrows) a ₁₁, c ₁₁, e ₁₁ and at age 12 by a ₂₁, c ₂₁, and e ₂₁. The second set of latent factors influence the phenotype at age 12 only, and is represented by the path coefficients a ₂₂, c ₂₂, and e ₂₂. The triangle represents the developmental change for height or the different brain volumes.

Figure 2

Absolute brain volume of total cerebral volume (A), cerebral gray matter (B), cerebral white matter (C), and total cerebellar volume (D) are given on all included subjects at baseline and follow‐up. Longitudinal data points are connected, and boys are depicted in blue, and girls in red.