Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment.
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 lang...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Blackwell Publishing Ltd
2014
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| _version_ | 1797099885466484736 |
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| author | Nudel, R Simpson, N Baird, G O'Hare, A Conti-Ramsden, G Bolton, P Hennessy, E Ring, S Davey Smith, G Francks, C Paracchini, S Monaco, A Fisher, SE Newbury, D |
| author_facet | Nudel, R Simpson, N Baird, G O'Hare, A Conti-Ramsden, G Bolton, P Hennessy, E Ring, S Davey Smith, G Francks, C Paracchini, S Monaco, A Fisher, SE Newbury, D |
| author_sort | Nudel, R |
| collection | OXFORD |
| description | 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(-8)) and suggestive maternal parent-of-origin effects on chromosome 5p13 (P = 1.16 × 10(-7)). 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. |
| first_indexed | 2024-03-07T05:29:58Z |
| format | Journal article |
| id | oxford-uuid:e1e9ece2-a3ad-4f25-afe2-40c0950388e9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:29:58Z |
| publishDate | 2014 |
| publisher | Blackwell Publishing Ltd |
| record_format | dspace |
| spelling | oxford-uuid:e1e9ece2-a3ad-4f25-afe2-40c0950388e92022-03-27T09:57:29ZGenome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e1e9ece2-a3ad-4f25-afe2-40c0950388e9EnglishSymplectic Elements at OxfordBlackwell Publishing Ltd2014Nudel, RSimpson, NBaird, GO'Hare, AConti-Ramsden, GBolton, PHennessy, ERing, SDavey Smith, GFrancks, CParacchini, SMonaco, AFisher, SENewbury, DSpecific 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(-8)) and suggestive maternal parent-of-origin effects on chromosome 5p13 (P = 1.16 × 10(-7)). 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. |
| spellingShingle | Nudel, R Simpson, N Baird, G O'Hare, A Conti-Ramsden, G Bolton, P Hennessy, E Ring, S Davey Smith, G Francks, C Paracchini, S Monaco, A Fisher, SE Newbury, D Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment. |
| title | Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment. |
| title_full | Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment. |
| title_fullStr | Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment. |
| title_full_unstemmed | Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment. |
| title_short | Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment. |
| title_sort | genome wide association analyses of child genotype effects and parent of origin effects in specific language impairment |
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