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01.12.2016 | Research | Ausgabe 1/2016 Open Access

Journal of Neurodevelopmental Disorders 1/2016

Investigating the effects of copy number variants on reading and language performance

Journal of Neurodevelopmental Disorders > Ausgabe 1/2016
Alessandro Gialluisi, Alessia Visconti, Erik G. Willcutt, Shelley D. Smith, Bruce F. Pennington, Mario Falchi, John C. DeFries, Richard K. Olson, Clyde Francks, Simon E. Fisher
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s11689-016-9147-8) contains supplementary material, which is available to authorized users.
Clyde Francks and Simon E. Fisher are joint senior authors.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

CF and SEF conceived and supervised the present study. AG performed the statistical analyses, genotype, and phenotype QC. AG, CF, and SEF designed the experiments and wrote the manuscript. AV and MF provided technical and theoretical assistance in FamCNV analysis and pre-analysis QC. SDS was responsible for DNA samples management. JCD, EGW, RKO, and BFP are CLDRC co-investigators (involved in the collection and preliminary elaboration of reading and language traits). All the authors contributed to the paper and approved the submitted version.



Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs).


In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes). Then, we computed the correlation between measures of CNV genomic burden and the first principal component (PC) score derived from several continuous reading and language traits, both before and after adjustment for performance IQ. Finally, we screened the genome, probe-by-probe, for association with the PC scores, through two complementary analyses: we tested a binary CNV state assigned for the location of each probe (i.e., CNV+ or CNV−), and we analyzed continuous probe intensity data using FamCNV.


No significant correlation was found between measures of CNV burden and PC scores, and no genome-wide significant associations were detected in probe-by-probe screening. Nominally significant associations were detected (p~10−2–10−3) within CNTN4 (contactin 4) and CTNNA3 (catenin alpha 3). These genes encode cell adhesion molecules with a likely role in neuronal development, and they have been previously implicated in autism and other neurodevelopmental disorders. A further, targeted assessment of candidate CNV regions revealed associations with the PC score (p~0.026–0.045) within CHRNA7 (cholinergic nicotinic receptor alpha 7), which encodes a ligand-gated ion channel and has also been implicated in neurodevelopmental conditions and language impairment. FamCNV analysis detected a region of association (p~10−2–10−4) within a frequent deletion ~6 kb downstream of ZNF737 (zinc finger protein 737, uncharacterized protein), which was also observed in the association analysis using CNV calls.


These data suggest that CNVs do not underlie a substantial proportion of variance in reading and language skills. Analysis of additional, larger datasets is warranted to further assess the potential effects that we found and to increase the power to detect CNV effects on reading and language.
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