Cortical Thickness Is Influenced by Regionally Specific Genetic Factors

Abstract

Background Although global brain structure is highly heritable, there is still variability in the magnitude of genetic influences on the size of specific regions. Yet, little is known about the patterning of those genetic influences, i.e., whether the same genes influence structure throughout the brain or whether there are regionally-specific sets of genes. Methods We mapped the heritability of cortical thickness throughout the brain using 3D structural magnetic resonance imaging in 404 middle-aged male twins. To assess the amount of genetic overlap between regions, we then mapped genetic correlations between three selected seed points and all other points comprising the continuous cortical surface. Results There was considerable regional variability in the magnitude of genetic influences on cortical thickness. The primary visual (V1) seed point had strong genetic correlations with posterior sensory and motor areas. The anterior temporal seed point had strong genetic correlations with anterior frontal regions, but not with V1. The middle frontal seed point had strong genetic correlations with inferior parietal regions. Conclusions These results provide strong evidence of regionally-specific patterns rather than a single, global genetic factor. The patterns are largely consistent with a division between primary and association cortex, as well as broadly-defined patterns of brain gene expression, neuroanatomical connectivity, and brain maturation trajectories, but no single explanation appears to be sufficient. The patterns do not conform to traditionally-defined brain structure boundaries. This approach can serve as a step toward identifying novel phenotypes for genetic association studies of psychiatric disorders, and normal and pathological cognitive aging.

Genetic topography of brain morphology

“…These regions are known to be structurally and functionally connected. This result is consistent with our previous report based on a limited seed-point analysis, which showed that the pattern of genetic correlations for cortical thickness partially correspond to neuroanatomical connectivity, with high genetic correlations between distal, noncontiguous regions (28). The cross-regional genetic patterning of cortical thickness may relate to underlying fiber tract structures (e.g., thalamocortical or intracortical connections).…”

“…Magnetic resonance (MR) images do not have sufficient spatial resolution to examine cortical thickness by each layer; instead, we measure the combined thickness across all cortical layers at each cortical location. We have previously explored the genetic patterning of cortical thickness based on three preselected cortical locations (seed points), and findings suggested that the genetic correlation pattern of cortical thickness differs from that of surface area, lacking the A-P or lobar divisions observed in the latter (28). This limited seed-point analysis made no attempt to define gradients or discover specific genetic boundaries, however.…”

Structural covariance of brain region volumes is associated with both structural connectivity and transcriptomic similarity

“…Such networks of anatomical change ("maturational coupling") are conjectured to 40 arise from the expression of common genetic cues during early development of the cortex (Raznahan et al, 2011). Supporting this are twin studies implicating genetics and structure (Schmitt et al, 2008;Rimol et al, 2010;Docherty et al, 2015), with one by Schmitt et al (2008) suggesting that the small-world network organization of structural covariance (He et al, 2007) might be explained by genetic correlations that display a similar pattern.…”

Surface‐based morphometry reveals distinct cortical thickness and surface area profiles in Williams syndrome

“…A possible explanation for these findings might be associated with the distinct genetic influences that control CT and SA in the human cortex [Panizzon et al, 2009;Rimol et al, 2010;Winkler et al, 2010]. Chen et al [2012Chen et al [ , 2013 compared brain development in neurotypical monozygotic and dizygotic twins to test the effect of genetic factors on SA and CT.…”