Quantitative tract-based white matter heritability in twin neonates

Abstract

Studies in adults indicate that white matter microstructure, assessed with diffusion tensor imaging (DTI), has high heritability. Little is known about genetic and environmental influences on DTI parameters, measured along fiber tracts particularly, in early childhood. In the present study, we report comprehensive heritability data of white matter microstructure fractional anisotropy (FA), radial diffusion (RD), and axial diffusion (AD) along 47 fiber tracts using the quantitative tractography in a large sample of neonatal twins (n=356). We found significant genetic influences in almost all tracts with similar heritabilities for FA, RD, and AD as well as positive relationships between these parameters and heritability. In a single tract analysis, genetic influences along the length of the tract were highly variable. These findings suggest that at birth, there is marked heterogeneity of genetic influences of white matter microstructure within white matter tracts. This study provides a basis for future studies of developmental changes in genetic and environmental influences during early childhood, a period of rapid development that likely plays a major role in individual differences in white matter structure and function.

Keywords: Axial diffusivity; Diffusion tensor imaging (DTI); Fractional anisotropy; Genetics; Quantitative tractography; Radial diffusivity.

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Fig. 1

Relationship between genetic contribution estimates of AD, RD, and FA for 43 tracts. The x-axis, y-axis, and the radius of each circle represent the estimates of AD, RD, and FA, respectively. Bilateral optic tracts and medial lemniscal pathways were not shown in this graph. SLF, superior longitudinal fasciculus; ILF, inferior longitudinal fasciculus; IFOF, inferior fronto-occipital fasciculus; UNC, uncinate fasciculus.

Fig. 2

Actual heritability plot of FA (A) and simplified versions of FA (B), AD (C), and RD (D) along tracts. In the graph B, C, and D, data points (x-axis) which showed significant heritability of FA, AD, and RD are highlighted in red, blue, and pink, respectively, on the mean value of each diffusion parameter (y-axis) along the individual tract. For real values for AD and RD, values on the y-axis are multiplied by 10−2.

Fig. 3

Statistically significant heritability estimates of FA along each tract for representative fibers. The genu and the splenium (A), the inferior longitudinal fasciculus (B), the inferior fronto-occipital fasciculus (C), and the fornix (D). The color bar shows heritability estimates of the FA. Heritability estimates with significance are highlighted; non-significant portions are white.

Fig. 4

Statistically significant heritability estimates of the FA along the left prefrontal bundle of the corticofugal fibers at different anatomical levels of the tract. The color bar shows heritability estimates of the FA. ACR, anterior corona radiata; ALIC, anterior limb of internal capsule; PLIC, posterior limb of internal capsule; CP, cerebral peduncle.

Fig. 5

Correlation plots of FA, AD, and RD and their heritability estimates within single tracts. Heritability (a2) and p-value of the tract-averaged FA along the length of a given tract are indicated in the parenthesis under the name of the tract. As the heritability of the tract increases from cingulate bundle to splenium, their FA and a2 also tend to increase. The corticofugal bundle and the cingulate gyrus bundle are on the left and right side of the brain respectively. CC, corpus callosum; IFOF, inferior fronto-occipital fasciculus.