Distinct genetic influences on cortical surface area and cortical thickness

Abstract

Neuroimaging studies examining the effects of aging and neuropsychiatric disorders on the cerebral cortex have largely been based on measures of cortical volume. Given that cortical volume is a product of thickness and surface area, it is plausible that measures of volume capture at least 2 distinct sets of genetic influences. The present study aims to examine the genetic relationships between measures of cortical surface area and thickness. Participants were men in the Vietnam Era Twin Study of Aging (110 monozygotic pairs and 92 dizygotic pairs). Mean age was 55.8 years (range: 51-59). Bivariate twin analyses were utilized in order to estimate the heritability of cortical surface area and thickness, as well as their degree of genetic overlap. Total cortical surface area and average cortical thickness were both highly heritable (0.89 and 0.81, respectively) but were essentially unrelated genetically (genetic correlation = 0.08). This pattern was similar at the lobar and regional levels of analysis. These results demonstrate that cortical volume measures combine at least 2 distinct sources of genetic influences. We conclude that using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure.

Figure 1.

Bivariate correlated factors model. (A) Additive genetic influences. (C) Shared or common environmental influences. (E) Nonshared or unique environmental influences. r_g = Genetic correlation; r_c = shared environment correlation; r_e = Unique environment correlation. Arrows from (A₁), (C₁), and (E₁) to surface area represent parameter estimates for the contribution of those components to the variable. The same is true for arrows from (A₂), (C₂), and (E₂) to cortical thickness. Squaring these parameter estimates provides the proportion of variance accounted for by each component.