Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Apr;14(4):377-85.
doi: 10.1111/gbb.12214. Epub 2015 Apr 8.

The DYX2 locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains

J D Eicher  1 , C M Stein, F Deng, A A Ciesla, N R Powers, R Boada, S D Smith, B F Pennington, S K Iyengar, B A Lewis, J R Gruen
Affiliations

The DYX2 locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains

J D Eicher et al. Genes Brain Behav. 2015 Apr.

Abstract

A major milestone of child development is the acquisition and use of speech and language. Communication disorders, including speech sound disorder (SSD), can impair a child's academic, social and behavioral development. Speech sound disorder is a complex, polygenic trait with a substantial genetic component. However, specific genes that contribute to SSD remain largely unknown. To identify associated genes, we assessed the association of the DYX2 dyslexia risk locus and markers in neurochemical signaling genes (e.g., nicotinic and dopaminergic) with SSD and related endophenotypes. We first performed separate primary associations in two independent samples - Cleveland SSD (210 affected and 257 unaffected individuals in 127 families) and Denver SSD (113 affected individuals and 106 unaffected individuals in 85 families) - and then combined results by meta-analysis. DYX2 markers, specifically those in the 3' untranslated region of DCDC2 (P = 1.43 × 10(-4) ), showed the strongest associations with phonological awareness. We also observed suggestive associations of dopaminergic-related genes ANKK1 (P = 1.02 × 10(-2) ) and DRD2 (P = 9.22 × 10(-3) ) and nicotinic-related genes CHRNA3 (P = 2.51 × 10(-3) ) and BDNF (P = 8.14 × 10(-3) ) with case-control status and articulation. Our results further implicate variation in putative regulatory regions in the DYX2 locus, particularly in DCDC2, influencing language and cognitive traits. The results also support previous studies implicating variation in dopaminergic and nicotinic neural signaling influencing human communication and cognitive development. Our findings expand the literature showing genetic factors (e.g., DYX2) contributing to multiple related, yet distinct neurocognitive domains (e.g., dyslexia, language impairment, and SSD). How these factors interactively yield different neurocognitive and language-related outcomes remains to be elucidated.

Keywords: DCDC2; DYX2; dopaminergic; nicotinic; speech sound disorder.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Amos, C.I. , Wu, X. , Broderick, P. , GOrloc, I.P. , Gu, J. , Eisen, T. , Dong, Q. , Zhang, Q. , Gu, X. , Vijayakrishnan, J. , Sullivan, K. , Matakidou, A. , Wang, Y. , Mills, G. , Doheny, K. , Tsai, Y.Y. , Chen, W.V. , Shete, S. , Spitz, M.R. & Houlston, R.S. (2008) Genome‐wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 40, 616–622. - PMC - PubMed
    1. ASHA Website . (2015) URL http://www.asha.org/public/speech/disorders/SpeechSoundDisorders/
    1. Bath, K.G. & Lee, F.S. (2006) Variant BDNF (Val66Met) on brain structure and function. Cogn Affect Behav Neurosci 6, 79–85. - PubMed
    1. Beaver, K.M. , Delisi, M. , Vaughn, M.G. & Wright, J.P. (2010) Association between the A1 allele of the DRD2 gene and reduced verbal abilities in adolescence and early adulthood. J Neural Transm 117, 827–830. - PubMed
    1. Becker, J. , Czamara, D. , Scerri, T.S. et al (2014) Genetic analysis of dyslexia candidate genes in the European cross‐linguistic NeuroDys cohort. Eur J Hum Genet 22, 675–680. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources