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

John D. Eicher, Angela M. Montgomery, Natacha Akshoomoff, David G. Amaral, Cinnamon S. Bloss, Ondrej Libiger, Nicholas J. Schork, Burcu F. Darst, B. J. Casey, Linda Chang, Thomas Ernst, Jean Frazier, Walter E. Kaufmann, Brian Keating, Tal Kenet, David Kennedy, Stewart H Mostofsky, Sarah S. Murray, Elizabeth R. Sowell, Hauke Bartsch & 6 others Joshua M. Kuperman, Timothy T. Brown, Donald J. Hagler, Anders M. Dale, Terry L. Jernigan, Jeffrey R. Gruen

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)272-282
Number of pages11
JournalBrain Imaging and Behavior
Volume10
Issue number1
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Fingerprint

Dyslexia
Genetic Markers
Neuroimaging
Language
Anisotropy
Reading
Temporal Lobe
Prefrontal Cortex
White Matter
Linear Models
Genotype
Pediatrics
Gene Expression
Genes

Keywords

  • Dyslexia
  • DYX2
  • DYX3
  • Imaging-genetics
  • KIAA0319
  • Language impairment

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Behavioral Neuroscience
  • Cellular and Molecular Neuroscience
  • Cognitive Neuroscience
  • Neurology
  • Psychiatry and Mental health
  • Clinical Neurology

Cite this

Eicher, J. D., Montgomery, A. M., Akshoomoff, N., Amaral, D. G., Bloss, C. S., Libiger, O., ... Gruen, J. R. (2016). Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children. Brain Imaging and Behavior, 10(1), 272-282. https://doi.org/10.1007/s11682-015-9392-6

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

In: Brain Imaging and Behavior, Vol. 10, No. 1, 01.03.2016, p. 272-282.

Research output: Contribution to journalArticle

Eicher, JD, Montgomery, AM, Akshoomoff, N, Amaral, DG, Bloss, CS, Libiger, O, Schork, NJ, Darst, BF, Casey, BJ, Chang, L, Ernst, T, Frazier, J, Kaufmann, WE, Keating, B, Kenet, T, Kennedy, D, Mostofsky, SH, Murray, SS, Sowell, ER, Bartsch, H, Kuperman, JM, Brown, TT, Hagler, DJ, Dale, AM, Jernigan, TL & Gruen, JR 2016, 'Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children', Brain Imaging and Behavior, vol. 10, no. 1, pp. 272-282. https://doi.org/10.1007/s11682-015-9392-6
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 H ; 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. / Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children. In: Brain Imaging and Behavior. 2016 ; Vol. 10, No. 1. pp. 272-282.
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