Exploring Genetic and Neural Risk of Specific Reading Disability within a Nuclear Twin Family Case Study: A Translational Clinical Application

Abstract

Imaging and genetic studies have characterized biological risk factors contributing to specific reading disability (SRD). The current study aimed to apply this literature to a family of twins discordant for SRD and an older sibling with reading difficulty. Intraclass correlations were used to understand the similarity of imaging phenotypes between pairs. Reading-related genes and brain region phenotypes, including asymmetry indices representing the relative size of left compared to right hemispheric structures, were descriptively examined. SNPs that corresponded between the SRD siblings and not the typically developing (TD) siblings were in genes ZNF385D, LPHN3, CNTNAP2, FGF18, NOP9, CMIP, MYO18B, and RBFOX2. Imaging phenotypes were similar among all sibling pairs for grey matter volume and surface area, but cortical thickness in reading-related regions of interest (ROIs) was more similar among the siblings with SRD, followed by the twins, and then the TD twin and older siblings, suggesting cortical thickness may differentiate risk for this family. The siblings with SRD had more symmetry of cortical thickness in the transverse temporal and superior temporal gyri, while the TD sibling had greater rightward asymmetry. The TD sibling had a greater leftward asymmetry of grey matter volume and cortical surface area in the fusiform, supramarginal, and transverse temporal gyrus. This exploratory study demonstrated that reading-related risk factors appeared to correspond with SRD within this family, suggesting that early examination of biological factors may benefit early identification. Future studies may benefit from the use of polygenic risk scores or machine learning to better understand SRD risk.

Keywords: genetics; neuroimaging; reading disability.

Figure 1

Composite images constructed from the MRI data for the supramarginal gyrus. (a) Masked areas are superimposed over anatomy in Freesurfer, on left. (b) Composite images constructed from layering many such masks are shown on the right. Each column shows the composite images of one sibling: the older sibling (OS) and the twins (TD Twin and Proband), respectively; rows represent the three anatomic axes. Images are semi-transparent such that brighter areas indicate higher volume areas—or more precisely, a brighter pixel is one that was present in a greater number of mask slices. Colorization is arbitrary and is used in masking to visually differentiate the mask from the underlying grayscale MRI image; grayscale versions were used in analysis.

Figure 2

Plots of cortical thickness asymmetry for each sibling.

Figure 3

Plots of cortical thickness in the transverse temporal gyrus and superior temporal gyrus.

Figure 4

Plots of grey matter volume in the fusiform gyrus and supramarginal gyrus.

Figure 5

Plots of cortical surface area in the fusiform gyrus, supramarginal gyrus, and transverse temporal gyrus.

Figure 6

Q–Q plots of sibling comparisons of regions in the ventral pathway.

Figure 7

Q–Q plots of region of interest comparisons for regions in the ventral pathway.

Figure 8

Select Q–Q plots of sibling comparisons of regions in the dorsal pathway.

Figure 9

Select Q–Q plots of region of interest comparisons for regions in the dorsal pathway.

Figure 10

Q–Q plots of sibling comparisons of regions in the frontal pathway.

Figure 11

Q–Q plots of region of interest comparisons for regions in the frontal pathway.