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Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children.

ABSTRACT: Dyslexia and language impairment (LI) are complex traits with substantial genetic components. We recently completed an association scan of the DYX2 locus, where we observed associations of markers in DCDC2, KIAA0319, ACOT13, and FAM65B with reading-, language-, and IQ-related traits. Additionally, the effects of reading-associated DYX3 markers were recently characterized using structural neuroimaging techniques. Here, we assessed the neuroimaging implications of associated DYX2 and DYX3 markers, using cortical volume, cortical thickness, and fractional anisotropy. To accomplish this, we examined eight DYX2 and three DYX3 markers in 332 subjects in the Pediatrics Imaging Neurocognition Genetics study. Imaging-genetic associations were examined by multiple linear regression, testing for influence of genotype on neuroimaging. Markers in DYX2 genes KIAA0319 and FAM65B were associated with cortical thickness in the left orbitofrontal region and global fractional anisotropy, respectively. KIAA0319 and ACOT13 were suggestively associated with overall fractional anisotropy and left pars opercularis cortical thickness, respectively. DYX3 markers showed suggestive associations with cortical thickness and volume measures in temporal regions. Notably, we did not replicate association of DYX3 markers with hippocampal measures. In summary, we performed a neuroimaging follow-up of reading-, language-, and IQ-associated DYX2 and DYX3 markers. DYX2 associations with cortical thickness may reflect variations in their role in neuronal migration. Furthermore, our findings complement gene expression and imaging studies implicating DYX3 markers in temporal regions. These studies offer insight into where and how DYX2 and DYX3 risk variants may influence neuroimaging traits. Future studies should further connect the pathways to risk variants associated with neuroimaging/neurocognitive outcomes.

SUBMITTER: Eicher JD

PROVIDER: S-EPMC4639472 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children.

Eicher John D JD Montgomery Angela M AM Akshoomoff Natacha N Amaral David G DG Bloss Cinnamon S CS Libiger Ondrej O Schork Nicholas J NJ Darst Burcu F BF Casey B J BJ Chang Linda L Ernst Thomas T Frazier Jean J Kaufmann Walter E WE Keating Brian B Kenet Tal T Kennedy David D Mostofsky Stewart S Murray Sarah S SS Sowell Elizabeth R ER Bartsch Hauke H Kuperman Joshua M JM Brown Timothy T TT Hagler Donald J DJ Dale Anders M AM Jernigan Terry L TL Gruen Jeffrey R JR

Brain imaging and behavior 20160301 1

Dyslexia and language impairment (LI) are complex traits with substantial genetic components. We recently completed an association scan of the DYX2 locus, where we observed associations of markers in DCDC2, KIAA0319, ACOT13, and FAM65B with reading-, language-, and IQ-related traits. Additionally, the effects of reading-associated DYX3 markers were recently characterized using structural neuroimaging techniques. Here, we assessed the neuroimaging implications of associated DYX2 and DYX3 markers, ...[more]

PMID: 25953057

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Project description:Background and purpose: Previous voxel-based morphometry (VBM) studies have suggested that cortical atrophy is regionally distributed in middle-aged subjects with white matter hyperintense (WMH) lesions. However, few studies have assessed cortical thickness in middle-aged WMH subjects. In this study, we examined cortical thickness as well as cortical morphometry associated with the presence of WMH lesion load in middle-aged subjects. Participants and methods: Thirty-six middle-aged subjects with WMH lesions (WMH group) and without clinical cognitive impairment, and 34 demographically matched healthy control subjects (HCS group) participated in the study. Cortical thickness was estimated using an automated Computational Anatomy Toolbox (CAT12) as the distance between the gray-white matter border and the pial surface. Individual WMH lesions were manually segmented, and WMH loads were measured. Statistical cortical maps were created to estimate differences in cortical thickness between groups based on this cortex-wide analysis. The relationship between WMH lesion loads and cerebral cortical thickness was also analyzed in CAT12. Results: Cortical thickness was significantly lower in the WMH group than in the controls in multimodal integration regions, including the right and left dorsal anterior cingulate cortex (dACC), right and left frontal operculum (fO), right and left operculum parietale (OP), right and left middle temporal gyrus (MTG), and left superior temporal gyrus (STG; P < 0.01, family-wise error (FWE)-corrected). Additionally, cortical thickness was also lower in the recognition regions that contained the right temporal pole (TP), the right and left fusiform gyrus, and the left rolandic operculum (RO; P < 0.01, FWE-corrected). The results revealed that in the left superior parietal lobule (SPL), cortical thickness was higher in the WMH group than in the HCS group (P < 0.01, FWE-corrected). A voxel-wise negative correlation was found between cortical thickness and WMH lesion loads in the right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex (DLPFC), and right subcallosal cortex (P < 0.01, FWE-corrected). Conclusion: The main findings of this study suggest that middle-aged WMH subjects are more likely to exhibit cortical thinning, especially in multimodal integration and recognition- and motor-related regions. The current morphometry data provide further evidence for WMH-associated structural plasticity.

Dataset Information

Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children.

Publications

Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children.

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