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Working-memory endophenotype and dyslexia-associated genetic variant predict dyslexia phenotype
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Männel, Claudia, Meyer, Lars, Wilcke, Arndt, Boltze, Johannes, Kirsten, Holger and Friederici, Angela D. (2015) Working-memory endophenotype and dyslexia-associated genetic variant predict dyslexia phenotype. Cortex, 71 . pp. 291-305. doi:10.1016/j.cortex.2015.06.029 ISSN 0010-9452.
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Official URL: http://dx.doi.org/10.1016/j.cortex.2015.06.029
Abstract
Developmental dyslexia, a severe impairment of literacy acquisition, is known to have a neurological basis and a strong genetic background. However, effects of individual genetic variations on dyslexia-associated deficits are only moderate and call for the assessment of the genotype’s impact on mediating neuro-endophenotypes by the imaging genetics approach. Using voxel-based morphometry (VBM) in German participants with and without dyslexia, we investigated gray matter changes and their association with impaired phonological processing, such as reduced verbal working memory. These endophenotypical alterations were, together with dyslexia-associated genetic variations, examined on their suitability as potential predictors of dyslexia. We identified two gray matter clusters in the left posterior temporal cortex related to verbal working memory capacity. Regional cluster differences correlated with genetic risk variants in TNFRSF1B. High-genetic-risk participants exhibit a structural predominance of auditory-association areas relative to auditory-sensory areas, which may partly compensate for deficient early auditory-sensory processing stages of verbal working memory. The reverse regional predominance observed in low-genetic-risk participants may in turn reflect reliance on these early auditory-sensory processing stages. Logistic regression analysis further supported that regional gray matter differences and genetic risk interact in the prediction of individuals' diagnostic status: With increasing genetic risk, the working-memory related structural predominance of auditory-association areas relative to auditory-sensory areas classifies participants with dyslexia versus control participants. Focusing on phonological deficits in dyslexia, our findings suggest endophenotypical changes in the left posterior temporal cortex could comprise novel pathomechanisms for verbal working memory-related processes translating TNFRSF1B genotype into the dyslexia phenotype.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
| Journal or Publication Title: | Cortex | ||||
| Publisher: | Elsevier Masson | ||||
| ISSN: | 0010-9452 | ||||
| Official Date: | October 2015 | ||||
| Dates: |
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| Volume: | 71 | ||||
| Page Range: | pp. 291-305 | ||||
| DOI: | 10.1016/j.cortex.2015.06.029 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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