Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment.

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

Journal article

Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment.

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 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.

Publication status:: Published

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APA Style

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, S. E., & Newbury, D. (2014). Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment. Genes, Brain, and Behavior, 13(4), 418–429.

MLA Style

Nudel, R., et al. “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, Blackwell Publishing Ltd, 2014, pp. 418–29.

Chicago Style

Nudel, R, N Simpson, G Baird, A O'Hare, G Conti-Ramsden, P Bolton, E Hennessy, et al. 2014. “Genome-Wide Association Analyses of Child Genotype Effects and Parent-of-Origin Effects in Specific Language Impairment.” Genes, Brain, and Behavior 13 (4): 418–29.
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