Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Pettigrew, Kerry; Frinton, Emily; Nudel, Ron; Chan, May; Thompson, Paul; Hayiou-Thomas, Marianna; Talcott, Joel; Stein, John; Monaco, Anthony; Hulme, Charles; Snowling, Margaret; Newbury, Dianne; Paracchini, Silvia
• Is Part Of: Journal of neurodevelopmental disorders. Volume 8:Issue 1(2016)
• Page Start: 1
• Page End: 8
• Publication Date: 2016-12
• Subjects: Language impairment -- Dyslexia -- Genetic association -- Parent-of-origin -- Candidate gene; Developmental neurobiology -- Periodicals; Neurosciences -- Periodicals; Nervous system -- Diseases -- Periodicals; 618.928
• DOI: 10.1186/s11689-016-9157-6
• Languages: English
• ISSNs: 1866-1947

Abstract

Abstract Background Specific language impairment (SLI) is a common neurodevelopmental disorder, observed in 5–10 % of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have been reported to date. A recent genome-wide association study (GWAS) described the first statistically significant association specifically for a SLI cohort between a missense variant (rs4280164) in theNOP9 gene and language-related phenotypes under a parent-of-origin model. Replications of these findings are particularly challenging because the availability of parental DNA is required. Methods We used two independent family-based cohorts characterised with reading- and language-related traits: a longitudinal cohort (n = 106 informative families) including children with language and reading difficulties and a nuclear family cohort (n = 264 families) selected for dyslexia. Results We observed association with language-related measures when modelling for parent-of-origin effects at theNOP9 locus in both cohorts: minimumP = 0.001 for phonological awareness with a paternal effect in the first cohort and minimumP = 0.0004 for irregular word reading with a maternal effect in the second cohort. Allelic and parental trends were not consistent when compared to the original study. Conclusions A parent-of-origin effect at this locus was detected in both cohorts, albeit with different trends. These findings contribute in interpreting the original GWAS report and support further investigations of theNOP9 locus and its role in language-related traits. A systematic evaluation of parent-of-origin effects in genetic association studies has the potential to reveal novel mechanisms underlying complex traits.