Show simple item record

Files in this item


Item metadata

dc.contributor.authorNudel, Ron
dc.contributor.authorSimpson, Nuala H
dc.contributor.authorBaird, Gillian
dc.contributor.authorO'Hare, Anne
dc.contributor.authorConti-Ramsden, Gina
dc.contributor.authorBolton, Patrick F
dc.contributor.authorHennessy, Elizabeth R
dc.contributor.authorRing, Susan M
dc.contributor.authorSmith, George Davey
dc.contributor.authorFrancks, Clyde
dc.contributor.authorParacchini, Silvia
dc.contributor.authorMonaco, Anthony P
dc.contributor.authorFisher, Simon E
dc.contributor.authorNewbury, Dianne F
dc.contributor.authorThe SLI Consortium
dc.identifier.citationNudel , 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 .
dc.identifier.otherPURE: 100676026
dc.identifier.otherPURE UUID: 25e105d4-0ec1-413d-828a-82c4b50a32a4
dc.identifier.otherPubMed: 24571439
dc.identifier.otherScopus: 84897958382
dc.identifier.otherORCID: /0000-0001-9934-8602/work/60428107
dc.identifier.otherWOS: 000333887500007
dc.descriptionDianne 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.abstractSpecific 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.relation.ispartofGenes, Brain and Behavioren
dc.rights© 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en
dc.subjectNeurodevelopmental disorderen
dc.subjectSpecific language impairmenten
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectQH426 Geneticsen
dc.titleGenome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairmenten
dc.typeJournal articleen
dc.contributor.sponsorThe Royal Societyen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.description.statusPeer revieweden

This item appears in the following Collection(s)

Show simple item record