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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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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639472/
https://www.ncbi.nlm.nih.gov/pubmed/25953057
http://dx.doi.org/10.1007/s11682-015-9392-6
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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.
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.
collection PubMed
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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11682-015-9392-6) contains supplementary material, which is available to authorized users.
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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. Brain Imaging Behav 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11682-015-9392-6) contains supplementary material, which is available to authorized users. 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.
spellingShingle Original Research
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
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639472/
https://www.ncbi.nlm.nih.gov/pubmed/25953057
http://dx.doi.org/10.1007/s11682-015-9392-6
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