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Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment
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dc.contributor.author | Nudel, Ron | |
dc.contributor.author | Simpson, Nuala H | |
dc.contributor.author | Baird, Gillian | |
dc.contributor.author | O'Hare, Anne | |
dc.contributor.author | Conti-Ramsden, Gina | |
dc.contributor.author | Bolton, Patrick F | |
dc.contributor.author | Hennessy, Elizabeth R | |
dc.contributor.author | Ring, Susan M | |
dc.contributor.author | Smith, George Davey | |
dc.contributor.author | Francks, Clyde | |
dc.contributor.author | Paracchini, Silvia | |
dc.contributor.author | Monaco, Anthony P | |
dc.contributor.author | Fisher, Simon E | |
dc.contributor.author | Newbury, Dianne F | |
dc.contributor.author | The SLI Consortium | |
dc.date.accessioned | 2015-12-04T11:10:02Z | |
dc.date.available | 2015-12-04T11:10:02Z | |
dc.date.issued | 2014-04 | |
dc.identifier | 100676026 | |
dc.identifier | 25e105d4-0ec1-413d-828a-82c4b50a32a4 | |
dc.identifier | 24571439 | |
dc.identifier | 84897958382 | |
dc.identifier | 000333887500007 | |
dc.identifier.citation | Nudel , R , Simpson , N H , Baird , G , O'Hare , A , Conti-Ramsden , G , Bolton , P F , Hennessy , E R , Ring , S M , Smith , G D , Francks , C , Paracchini , S , Monaco , A P , Fisher , S E , Newbury , D F & The SLI Consortium 2014 , ' Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment ' , Genes, Brain and Behavior , vol. 13 , no. 4 , pp. 418–429 . https://doi.org/10.1111/gbb.12127 | en |
dc.identifier.issn | 1601-1848 | |
dc.identifier.other | ORCID: /0000-0001-9934-8602/work/60428107 | |
dc.identifier.uri | https://hdl.handle.net/10023/7888 | |
dc.description | Dianne Newbury is an MRC Career Development Fellow and a Junior Research Fellow at St John’s College, University of Oxford. The work of the Newbury lab is funded by the Medical Research Council [G1000569/1 and MR/J003719/1]. Ron Nudel is funded by a University of Oxford Nuffield Department of Medicine Prize Studentship. The genotyping of samples was funded by the Max Planck Society. Silvia Paracchini is a Royal Society University Research Fellow. The analyses of the ALSPAC cohort were supported by a grant from the Medical Research Council [G0800523/86473]. The collection of the SLIC samples was supported by the Wellcome Trust (060774 and 076566). Patrick Bolton is supported by a National Institute of Health Research (UK) Senior Investigator award and the Biomedical Research Centre in Mental Health at the South London & Maudsley NHS Trust Hospital, London. The work of the Wellcome Trust Centre in Oxford is supported by the Wellcome Trust [090532/Z/09/Z]. | en |
dc.description.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 × 10-8 ) 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 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 sum, 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. | |
dc.format.extent | 1025057 | |
dc.language.iso | eng | |
dc.relation.ispartof | Genes, Brain and Behavior | en |
dc.subject | ALSPAC | en |
dc.subject | GWAS | en |
dc.subject | Imprinting | en |
dc.subject | Neurodevelopmental disorder | en |
dc.subject | Specific language impairment | en |
dc.subject | RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry | en |
dc.subject | QH426 Genetics | en |
dc.subject.lcc | RC0321 | en |
dc.subject.lcc | QH426 | en |
dc.title | Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment | en |
dc.type | Journal article | en |
dc.contributor.sponsor | The Royal Society | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | 10.1111/gbb.12127 | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | UF100463 | en |
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