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Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment.
- Source :
- Genes, Brain & Behavior; Apr2014, Vol. 13 Issue 4, p418-429, 12p
- Publication Year :
- 2014
-
Abstract
- Specific language impairment ( SLI) is a neurodevelopmental disorder that affects linguistic abilities when development is otherwise normal. We report the results of a genome-wide association study of SLI which included parent-of-origin effects and child genotype effects and used 278 families of language-impaired children. The child genotype effects analysis did not identify significant associations. We found genome-wide significant paternal parent-of-origin effects on chromosome 14q12 ( P = 3.74 × 10<superscript>−8</superscript>) and suggestive maternal parent-of-origin effects on chromosome 5p13 ( P = 1.16 × 10<superscript>−7</superscript>). A subsequent targeted association of six single-nucleotide-polymorphisms ( SNPs) on chromosome 5 in 313 language-impaired individuals and their mothers from the ALSPAC cohort replicated the maternal effects, albeit in the opposite direction ( P = 0.001); as fathers' genotypes were not available in the ALSPAC study, the replication analysis did not include paternal parent-of-origin effects. The paternally-associated SNP on chromosome 14 yields a non-synonymous coding change within the NOP9 gene. This gene encodes an RNA-binding protein that has been reported to be significantly dysregulated in individuals with schizophrenia. The region of maternal association on chromosome 5 falls between the PTGER4 and DAB2 genes, in a region previously implicated in autism and ADHD. The top SNP in this association locus is a potential expression QTL of ARHGEF19 (also called WGEF) on chromosome 1. Members of this protein family have been implicated in intellectual disability. In summary, this study implicates parent-of-origin effects in language impairment, and adds an interesting new dimension to the emerging picture of shared genetic etiology across various neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16011848
- Volume :
- 13
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Genes, Brain & Behavior
- Publication Type :
- Academic Journal
- Accession number :
- 95466433
- Full Text :
- https://doi.org/10.1111/gbb.12127