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

• Published in: Brain imaging and behavior Vol. 10; no. 1; pp. 272 - 282
• Main Authors: Eicher, John D., Montgomery, Angela M., Akshoomoff, Natacha, Amaral, David G., Bloss, Cinnamon S., Libiger, Ondrej, Schork, Nicholas J., Darst, Burcu F., Casey, B. J., Chang, Linda, Ernst, Thomas, Frazier, Jean, Kaufmann, Walter E., Keating, Brian, Kenet, Tal, Kennedy, David, Mostofsky, Stewart, Murray, Sarah S., Sowell, Elizabeth R., Bartsch, Hauke, Kuperman, Joshua M., Brown, Timothy T., Hagler, Donald J., Dale, Anders M., Jernigan, Terry L., Gruen, Jeffrey R.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-03-2016; Springer Nature B.V
• Subjects: Adolescent; Anisotropy; Biomedical and Life Sciences; Biomedicine; Brain - diagnostic imaging; Brain - pathology; Cell Adhesion Molecules; Child; Child development; Child, Preschool; Children & youth; Cognition & reasoning; Cognitive ability; Cohort Studies; Cross-Sectional Studies; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Dyslexia; Dyslexia - diagnostic imaging; Dyslexia - genetics; Dyslexia - pathology; Genetic Predisposition to Disease; Genetics; Genotyping Techniques; Hospitals; Humans; Language Development Disorders - diagnostic imaging; Language Development Disorders - genetics; Language Development Disorders - pathology; Language disorders; Magnetic resonance imaging; Medical imaging; Medicine; Nerve Tissue Proteins - genetics; Neuroimaging; Neuropsychology; Neuroradiology; Neurosciences; Organ Size; Original Research; Pediatrics; Polymorphism, Single Nucleotide; Proteins - genetics; Psychiatry; Reading; Thiolester Hydrolases - genetics; White Matter - diagnostic imaging; White Matter - growth & development; White Matter - pathology; Young Adult; Los Angeles California; La Jolla California; California; United States > US; DYX3; Dyslexia; Language impairment; Imaging-genetics; DYX2; KIAA0319
• ISSN: 1931-7557; 1931-7565
• DOI: 10.1007/s11682-015-9392-6

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.