Elsevier

NeuroImage

Volume 49, Issue 2, 15 January 2010, Pages 1213-1223
NeuroImage

Genetic and environmental influences on the size of specific brain regions in midlife: The VETSA MRI study

https://doi.org/10.1016/j.neuroimage.2009.09.043Get rights and content

Abstract

The impact of genetic and environmental factors on human brain structure is of great importance for understanding normative cognitive and brain aging as well as neuropsychiatric disorders. However, most studies of genetic and environmental influences on human brain structure have either focused on global measures or have had samples that were too small for reliable estimates. Using the classical twin design, we assessed genetic, shared environmental, and individual-specific environmental influences on individual differences in the size of 96 brain regions of interest (ROIs). Participants were 474 middle-aged male twins (202 pairs; 70 unpaired) in the Vietnam Era Twin Study of Aging (VETSA). They were 51–59 years old, and were similar to U.S. men in their age range in terms of sociodemographic and health characteristics. We measured thickness of cortical ROIs and volume of other ROIs. On average, genetic influences accounted for approximately 70% of the variance in the volume of global, subcortical, and ventricular ROIs and approximately 45% of the variance in the thickness of cortical ROIs. There was greater variability in the heritability of cortical ROIs (0.00–0.75) as compared with subcortical and ventricular ROIs (0.48–0.85). The results did not indicate lateralized heritability differences or greater genetic influences on the size of regions underlying higher cognitive functions. The findings provide key information for imaging genetic studies and other studies of brain phenotypes and endophenotypes. Longitudinal analysis will be needed to determine whether the degree of genetic and environmental influences changes for different ROIs from midlife to later life.

Section snippets

Participants

An overview of the longitudinal VETSA project can be found elsewhere (Kremen et al., 2006). The study was approved by the Human Subjects Committees of all involved institutions, and all participants gave written informed consent. A total of 1237 twins participated in wave 1. They were randomly selected from a larger pool of individuals in a prior Vietnam Era Twin Registry study (Tsuang et al., 2001). Registry members are male–male twin pairs born between 1939 and 1957 who both served in the

Results

MZ and DZ correlations and the proportions of variance accounted for by genetic, shared environmental, and individual-specific environmental influences for each of the age, site, and TIV-adjusted volume-based ROIs are shown in Table 1. The same indices for the ROIs measured by thickness (adjusted for age and site only) are shown in Table 2 and in Fig. 3. MZ correlations were consistently higher than DZ correlations, suggesting genetic influences on the size of almost all ROIs. The full (ACE)

Discussion

To our knowledge, this is the first large-scale study to comprehensively examine genetic and environmental influences on the size of specific cortical, subcortical, and ventricular brain structures all in the same individuals. On average, about 70% of the variance in the size of subcortical ROIs and ventricles is determined by genetic factors. Cortical ROIs showed a moderate degree of genetic influence, accounting, on average, for about 45% of the variance in thickness. There was also greater

Acknowledgments

Funded by the National Institute on Aging (AG022381, AG018384, AG018386, AG022982); the National Center for Research Resources (P41-RR14075; NCRR BIRN Morphometric Project BIRN002); the National Institute for Biomedical Imaging and Bioengineering (R01EB006758); the National Institute for Neurological Disorders and Stroke (R01 NS052585-01); and the Mental Illness and Neuroscience Discovery (MIND) Institute, part of the National Alliance for Medical Image Computing (NAMIC), funded by the National

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