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

Autor: Eicher JD; Department of Genetics, Yale University, New Haven, CT, 06520, USA., Montgomery AM; Department of Pediatrics, Yale University School of Medicine, New Haven, CT, 06520, USA., Akshoomoff N; Center for Human Development, University of California, La Jolla, San Diego, CA, 92037, USA.; Department of Psychiatry, University of California, La Jolla, San Diego, CA, 92037, USA., Amaral DG; Department of Psychiatry and Behavioral Sciences, University of California, Davis, CA, 95817, USA., Bloss CS; Scripps Genomic Medicine, Scripps Health, Scripps Translational Science Institute, La Jolla, CA, 92037, USA., Libiger O; Scripps Genomic Medicine, Scripps Health, Scripps Translational Science Institute, La Jolla, CA, 92037, USA., Schork NJ; Scripps Genomic Medicine, Scripps Health, Scripps Translational Science Institute, La Jolla, CA, 92037, USA., Darst BF; Scripps Genomic Medicine, Scripps Health, Scripps Translational Science Institute, La Jolla, CA, 92037, USA., Casey BJ; Sackler Institute for Developmental Psychobiology, Weil Cornell Medical College, New York, NY, 10065, USA., Chang L; Department of Medicine, Queen's Medical Center, University of Hawaii, Honolulu, HI, 96813, USA., Ernst T; Department of Medicine, Queen's Medical Center, University of Hawaii, Honolulu, HI, 96813, USA., Frazier J; Department of Psychiatry, University of Massachusetts Medical School, Boston, MA, 01655, USA., Kaufmann WE; Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD, 21205, USA.; Department of Neurology, Harvard Medical School, Children's Hospital Boston, Boston, MA, 02115, USA., Keating B; Department of Medicine, Queen's Medical Center, University of Hawaii, Honolulu, HI, 96813, USA., Kenet T; Department of Neurology and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA., Kennedy D; Department of Psychiatry, University of Massachusetts Medical School, Boston, MA, 01655, USA., Mostofsky S; Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD, 21205, USA., Murray SS; Scripps Genomic Medicine, Scripps Health, Scripps Translational Science Institute, La Jolla, CA, 92037, USA., Sowell ER; Department of Pediatrics, University of Southern California, Los Angeles, CA, 90027, USA.; Developmental Cognitive Neuroimaging Laboratory Children's Hospital, Los Angeles, CA, 90027, USA., Bartsch H; Multimodal Imaging Laboratory, University of California, La Jolla, San Diego, CA, 92037, USA., Kuperman JM; Multimodal Imaging Laboratory, University of California, La Jolla, San Diego, CA, 92037, USA.; Department of Neurosciences, University of California, La Jolla, San Diego, CA, 92037, USA., Brown TT; Center for Human Development, University of California, La Jolla, San Diego, CA, 92037, USA.; Multimodal Imaging Laboratory, University of California, La Jolla, San Diego, CA, 92037, USA.; Department of Neurosciences, University of California, La Jolla, San Diego, CA, 92037, USA., Hagler DJ Jr; Multimodal Imaging Laboratory, University of California, La Jolla, San Diego, CA, 92037, USA.; Radiology University of California, La Jolla, San Diego, CA, 92037, USA., Dale AM; Department of Psychiatry, University of California, La Jolla, San Diego, CA, 92037, USA.; Multimodal Imaging Laboratory, University of California, La Jolla, San Diego, CA, 92037, USA.; Department of Neurosciences, University of California, La Jolla, San Diego, CA, 92037, USA.; Radiology University of California, La Jolla, San Diego, CA, 92037, USA.; Cognitive Science University of California, La Jolla, San Diego, CA, 92037, USA., Jernigan TL; Center for Human Development, University of California, La Jolla, San Diego, CA, 92037, USA.; Department of Psychiatry, University of California, La Jolla, San Diego, CA, 92037, USA.; Radiology University of California, La Jolla, San Diego, CA, 92037, USA.; Cognitive Science University of California, La Jolla, San Diego, CA, 92037, USA., Gruen JR; Department of Genetics, Yale University, New Haven, CT, 06520, USA. jeffrey.gruen@yale.edu.; Department of Pediatrics, Yale University School of Medicine, New Haven, CT, 06520, USA. jeffrey.gruen@yale.edu.; Department of Investigative, School of Medicine, Medicine Yale University, New Haven, CT, 06520, USA. jeffrey.gruen@yale.edu.; 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.
Jazyk: angličtina
Zdroj: Brain imaging and behavior [Brain Imaging Behav] 2016 Mar; Vol. 10 (1), pp. 272-82.
DOI: 10.1007/s11682-015-9392-6
Abstrakt: 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.
Databáze: MEDLINE
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