Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes


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 the NOP9 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 the NOP9 locus in both cohorts: minimum P = 0.001 for phonological awareness with a paternal effect in the first cohort and minimum P = 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 the NOP9 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.

Publication DOI: https://doi.org/10.1186/s11689-016-9157-6
Divisions: College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences
College of Health & Life Sciences > School of Optometry > Vision, Hearing and Language
College of Health & Life Sciences > Aston Institute of Health & Neurodevelopment (AIHN)
Additional Information: © 2016 The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Uncontrolled Keywords: language impairment,candidate gene,parent-of-origin,genetic association,dyslexia
Publication ISSN: 1866-1955
Last Modified: 29 Feb 2024 08:13
Date Deposited: 12 Sep 2016 11:10
PURE Output Type: Article
Published Date: 2016-06-14
Accepted Date: 2016-06-03
Submitted Date: 2015-12-07
Authors: Pettigrew, Kerry A.
Frinton, Emily
Nudel, Ron
Chan, May T.M.
Thompson, Paul
Hayiou-Thomas, Marianna E.
Talcott, Joel B. (ORCID Profile 0000-0001-7958-8369)
Stein, John
Monaco, Anthony P.
Hulme, Charles
Snowling, Margaret J.
Newbury, Dianne F.
Paracchini, Silvia



Version: Published Version

License: Creative Commons Attribution

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