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NPJ Sci Learn. 2018 Nov 21;3:20. doi: 10.1038/s41539-018-0034-9. eCollection 2018.

A molecular-genetic and imaging-genetic approach to specific comprehension difficulties in children.

Author information

1Department of Curriculum and Instruction, College of Education, University of Houston, Houston, TX USA.
2Graduate School of Education, Harvard University, Cambridge, MA USA.
3Department of Pediatrics, Yale University School of Medicine, New Haven, CT USA.
4Haskins Laboratories, New Haven, CT USA.
5Neurosciences and Mental Health Program, Learning Disabilities Research Program, The Hospital for Sick Children, University of Toronto, Toronto, ON Canada.
6Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT USA.
7Department of Genetics and the Investigative Medicine Program, Yale University School of Medicine, New Haven, CT USA.
8Faculty of Social Sciences, Department of Child and Youth Studies, Brock University, St. Catharines, ON Canada.
Contributed equally


Children with poor reading comprehension despite typical word reading skills were examined using neuropsychological, genetic, and neuroimaging data collected from the Genes, Reading and Dyslexia Study of 1432 Hispanic American and African American children. This unexpected poor comprehension was associated with profound deficits in vocabulary, when compared to children with comprehension skills consistent with their word reading. Those with specific comprehension difficulties were also more likely to have RU2Short alleles of READ1 regulatory variants of DCDC2, strongly associated with reading and language difficulties. Subjects with RU2Short alleles showed stronger resting state functional connectivity between the right insula/inferior frontal gyrus and the right supramarginal gyrus, even after controlling for potentially confounding variables including genetic ancestry and socioeconomic status. This multi-disciplinary approach advances the current understanding of specific reading comprehension difficulties, and suggests the need for interventions that are more appropriately tailored to the specific comprehension deficits of this group of children.

Conflict of interest statement

Yale University has applied for a patent covering the complex tandem repeat and microdeletion in READ1, also known as BV677278 (Inventor: J.R.G.). The remaining authors declare no competing interests.

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