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

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

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, t...

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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: Online
Language:English
Published: Springer US 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639472/
id pubmed-4639472
recordtype oai_dc
spelling pubmed-46394722016-03-08 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 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. Original Research 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. Springer US 2015-05-09 2016 /pmc/articles/PMC4639472/ /pubmed/25953057 http://dx.doi.org/10.1007/s11682-015-9392-6 Text en © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author 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.
spellingShingle 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.
Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children
author_facet 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.
author_sort Eicher, John D.
title Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children
title_short Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children
title_full Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children
title_fullStr Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children
title_full_unstemmed Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children
title_sort dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children
description 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.
publisher Springer US
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639472/
_version_ 1613499247179595776

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