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

John D Eicher¹, Angela M Montgomery², Natacha Akshoomoff^{3

4}, David G Amaral⁵, Cinnamon S Bloss⁶, Ondrej Libiger⁶, Nicholas J Schork⁶, Burcu F Darst⁶, B J Casey⁷, Linda Chang⁸, Thomas Ernst⁸, Jean Frazier⁹, Walter E Kaufmann^{10

11}, Brian Keating⁸, Tal Kenet¹², David Kennedy⁹, Stewart Mostofsky¹⁰, Sarah S Murray⁶, Elizabeth R Sowell^{13

14}, Hauke Bartsch¹⁵, Joshua M Kuperman^{15

16}, Timothy T Brown^{3

15

16}, Donald J Hagler Jr^{15

17}, Anders M Dale^{4

15

16

17

18}, Terry L Jernigan^{3

4

17

18}, Jeffrey R Gruen^{19

20

21

22}; Pediatric Imaging Neurocognition Genetics Study

Affiliations

¹ Department of Genetics, Yale University, New Haven, CT, 06520, USA.
² Department of Pediatrics, Yale University School of Medicine, New Haven, CT, 06520, USA.
³ Center for Human Development, University of California, La Jolla, San Diego, CA, 92037, USA.
⁴ Department of Psychiatry, University of California, La Jolla, San Diego, CA, 92037, USA.
⁵ Department of Psychiatry and Behavioral Sciences, University of California, Davis, CA, 95817, USA.
⁶ Scripps Genomic Medicine, Scripps Health, Scripps Translational Science Institute, La Jolla, CA, 92037, USA.
⁷ Sackler Institute for Developmental Psychobiology, Weil Cornell Medical College, New York, NY, 10065, USA.
⁸ Department of Medicine, Queen's Medical Center, University of Hawaii, Honolulu, HI, 96813, USA.
⁹ Department of Psychiatry, University of Massachusetts Medical School, Boston, MA, 01655, USA.
¹⁰ Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD, 21205, USA.
¹¹ Department of Neurology, Harvard Medical School, Children's Hospital Boston, Boston, MA, 02115, USA.
¹² Department of Neurology and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
¹³ Department of Pediatrics, University of Southern California, Los Angeles, CA, 90027, USA.
¹⁴ Developmental Cognitive Neuroimaging Laboratory Children's Hospital, Los Angeles, CA, 90027, USA.
¹⁵ Multimodal Imaging Laboratory, University of California, La Jolla, San Diego, CA, 92037, USA.
¹⁶ Department of Neurosciences, University of California, La Jolla, San Diego, CA, 92037, USA.
¹⁷ Radiology University of California, La Jolla, San Diego, CA, 92037, USA.
¹⁸ Cognitive Science University of California, La Jolla, San Diego, CA, 92037, USA.
¹⁹ Department of Genetics, Yale University, New Haven, CT, 06520, USA. jeffrey.gruen@yale.edu.
²⁰ Department of Pediatrics, Yale University School of Medicine, New Haven, CT, 06520, USA. jeffrey.gruen@yale.edu.
²¹ Department of Investigative, School of Medicine, Medicine Yale University, New Haven, CT, 06520, USA. jeffrey.gruen@yale.edu.
²² Department of Pediatrics, Genetics, and Investigative Medicine, Yale Child Health Research Center, 464 Congress Avenue, New Haven, CT, 06520-8081, USA. jeffrey.gruen@yale.edu.

PMID: 25953057
PMCID: PMC4639472
DOI: 10.1007/s11682-015-9392-6

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

John D Eicher et al. Brain Imaging Behav. 2016 Mar.

. 2016 Mar;10(1):272-82.

doi: 10.1007/s11682-015-9392-6.

Authors

Affiliations

¹ Department of Genetics, Yale University, New Haven, CT, 06520, USA.
² Department of Pediatrics, Yale University School of Medicine, New Haven, CT, 06520, USA.
³ Center for Human Development, University of California, La Jolla, San Diego, CA, 92037, USA.
⁴ Department of Psychiatry, University of California, La Jolla, San Diego, CA, 92037, USA.
⁵ Department of Psychiatry and Behavioral Sciences, University of California, Davis, CA, 95817, USA.
⁶ Scripps Genomic Medicine, Scripps Health, Scripps Translational Science Institute, La Jolla, CA, 92037, USA.
⁷ Sackler Institute for Developmental Psychobiology, Weil Cornell Medical College, New York, NY, 10065, USA.
⁸ Department of Medicine, Queen's Medical Center, University of Hawaii, Honolulu, HI, 96813, USA.
⁹ Department of Psychiatry, University of Massachusetts Medical School, Boston, MA, 01655, USA.
¹⁰ Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD, 21205, USA.
¹¹ Department of Neurology, Harvard Medical School, Children's Hospital Boston, Boston, MA, 02115, USA.
¹² Department of Neurology and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
¹³ Department of Pediatrics, University of Southern California, Los Angeles, CA, 90027, USA.
¹⁴ Developmental Cognitive Neuroimaging Laboratory Children's Hospital, Los Angeles, CA, 90027, USA.
¹⁵ Multimodal Imaging Laboratory, University of California, La Jolla, San Diego, CA, 92037, USA.
¹⁶ Department of Neurosciences, University of California, La Jolla, San Diego, CA, 92037, USA.
¹⁷ Radiology University of California, La Jolla, San Diego, CA, 92037, USA.
¹⁸ Cognitive Science University of California, La Jolla, San Diego, CA, 92037, USA.
¹⁹ Department of Genetics, Yale University, New Haven, CT, 06520, USA. jeffrey.gruen@yale.edu.
²⁰ Department of Pediatrics, Yale University School of Medicine, New Haven, CT, 06520, USA. jeffrey.gruen@yale.edu.
²¹ Department of Investigative, School of Medicine, Medicine Yale University, New Haven, CT, 06520, USA. jeffrey.gruen@yale.edu.
²² Department of Pediatrics, Genetics, and Investigative Medicine, Yale Child Health Research Center, 464 Congress Avenue, New Haven, CT, 06520-8081, USA. jeffrey.gruen@yale.edu.

PMID: 25953057
PMCID: PMC4639472
DOI: 10.1007/s11682-015-9392-6

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.

Keywords: DYX2; DYX3; Dyslexia; Imaging-genetics; KIAA0319; Language impairment.

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References

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

Affiliations

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

Authors

Affiliations

Abstract

References

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Substances

Grants and funding

LinkOut - more resources

Full Text Sources

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Miscellaneous