Distinct Genetic Influences on Cortical Surface Area and Cortical Thickness

TLDR

Neuroimaging studies of aging and neuropsychiatric disorders have largely relied on cortical volume, which is the product of thickness and surface area, suggesting that volume may mask distinct genetic influences on each component. This study investigates the genetic relationship between cortical surface area and cortical thickness. Using 110 monozygotic and 92 dizygotic twin pairs from the Vietnam Era Twin Study of Aging (mean age 55.8), the authors performed bivariate twin analyses to estimate heritability and genetic overlap of surface area and thickness. Both surface area and thickness were highly heritable (0.89 and 0.81) yet genetically uncorrelated (r = 0.08) across the cortex and at regional levels, indicating that cortical volume conflates at least two distinct genetic sources and may confound genetic studies of brain structure.

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.