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.
School of Medicine, University of St Andrews, St Andrews, KY16 9TF UK.
Kerry A
KA
Pettigrew
School of Medicine, University of St Andrews, St Andrews, KY16 9TF UK.
Emily
E
Frinton
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN UK.
Ron
R
Nudel
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN UK.|Worcester College, University of Oxford, Oxford, OX1 2HB UK.
May T M
MTM
Chan
Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford, OX1 3PT UK.
Paul
P
Thompson
Department of Psychology, University of York, York, YO10 5DD UK.
Marianna E
ME
Hayiou-Thomas
School of Life and Health Sciences, Aston University, Birmingham, B4 7ET UK.
Joel B
JB
Talcott
Department of Physiology, University of Oxford, Parks Road, Oxford, OX1 3PT UK.
John
J
Stein
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN UK.
Anthony P
AP
Monaco
Division of Psychology and Language Sciences, University College London, London, WC1 3PG UK.
Charles
C
Hulme
Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford, OX1 3PT UK.|St John's College, University of Oxford, Oxford, OX1 3JP UK.
Margaret J
MJ
Snowling
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN UK.
Dianne F
DF
Newbury
School of Medicine, University of St Andrews, St Andrews, KY16 9TF UK.
Silvia
S
Paracchini
Candidate gene; Dyslexia; Genetic association; Language impairment; Parent-of-origin