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

Kerry A. Pettigrew; Emily Frinton; Ron Nudel; May T.M. Chan; Paul Thompson; Marianna E. Hayiou-Thomas; Joel B. Talcott; John Stein; Anthony P. Monaco; Charles Hulme; Margaret J. Snowling; Dianne F. Newbury; Silvia Paracchini

doi:10.1186/s11689-016-9157-6

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

Kerry A. Pettigrew, Emily Frinton, Ron Nudel, May T.M. Chan, Paul Thompson, Marianna E. Hayiou-Thomas, Joel B. Talcott, John Stein, Anthony P. Monaco, Charles Hulme, Margaret J. Snowling, Dianne F. Newbury, Silvia Paracchini

Research output: Contribution to journal › Article › peer-review

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 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.

Original language	English
Article number	24
Number of pages	8
Journal	Journal of Neurodevelopmental Disorders
Volume	8
DOIs	https://doi.org/10.1186/s11689-016-9157-6
Publication status	Published - 14 Jun 2016

Bibliographical note

© 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.

Keywords

language impairment
candidate gene
parent-of-origin
genetic association
dyslexia

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10.1186/s11689-016-9157-6Licence: CC BY 3.0

Parent-of-origin effect at the NOP9 locus on language-related phenotypes
© 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.
Final published version, 443 KBLicence: CC BY 3.0

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Pettigrew, K. A., Frinton, E., Nudel, R., Chan, M. T. M., Thompson, P., Hayiou-Thomas, M. E., Talcott, J. B., Stein, J., Monaco, A. P., Hulme, C., Snowling, M. J., Newbury, D. F., & Paracchini, S. (2016). Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes. Journal of Neurodevelopmental Disorders, 8, Article 24. https://doi.org/10.1186/s11689-016-9157-6

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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 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.",

keywords = "language impairment, candidate gene, parent-of-origin, genetic association, dyslexia",

author = "Pettigrew, {Kerry A.} and Emily Frinton and Ron Nudel and Chan, {May T.M.} and Paul Thompson and Hayiou-Thomas, {Marianna E.} and Talcott, {Joel B.} and John Stein and Monaco, {Anthony P.} and Charles Hulme and Snowling, {Margaret J.} and Newbury, {Dianne F.} and Silvia Paracchini",

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doi = "10.1186/s11689-016-9157-6",

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TY - JOUR

T1 - Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes

AU - Pettigrew, Kerry A.

AU - Frinton, Emily

AU - Nudel, Ron

AU - Chan, May T.M.

AU - Thompson, Paul

AU - Hayiou-Thomas, Marianna E.

AU - Talcott, Joel B.

AU - Stein, John

AU - Monaco, Anthony P.

AU - Hulme, Charles

AU - Snowling, Margaret J.

AU - Newbury, Dianne F.

AU - Paracchini, Silvia

N1 - © 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.

PY - 2016/6/14

Y1 - 2016/6/14

N2 - 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.

AB - 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.

KW - language impairment

KW - candidate gene

KW - parent-of-origin

KW - genetic association

KW - dyslexia

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DO - 10.1186/s11689-016-9157-6

M3 - Article

C2 - 27307794

SN - 1866-1947

VL - 8

JO - Journal of Neurodevelopmental Disorders

JF - Journal of Neurodevelopmental Disorders

M1 - 24

ER -

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

Abstract

Bibliographical note

Keywords

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