UMMS Affiliation

Intellectual and Developmental Disabilities Research Center; Department of Psychiatry

Publication Date

2013-11

Document Type

Article

Subjects

Case-Control Studies; Cerebral Cortex; Child; Collagen Type IV; Dyslexia; Female; *Genome-Wide Association Study; Humans; Language Development Disorders; Longitudinal Studies; Male; Membrane Proteins; Polymorphism, Single Nucleotide; Sulfotransferases; Transcription Factors; Zinc Fingers

Disciplines

Behavioral Neurobiology | Communication Sciences and Disorders | Genomics | Mental Disorders | Psychiatry | Psychiatry and Psychology | Psycholinguistics and Neurolinguistics

Abstract

Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 x 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 x 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 x 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.

Keywords

ALSPAC, PING, ZNF385D, dyslexia GWAS, language impairment, reading disability

Rights and Permissions

© 2013 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley and Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

DOI of Published Version

10.1111/gbb.12085

Source

Eicher JD, Powers NR, Miller LL, Akshoomoff N, Amaral DG, Bloss CS, Libiger O, Schork NJ, Darst BF, Casey BJ, Chang L, Ernst T, Frazier J, Kaufmann WE, Keating B, Kenet T, Kennedy D, Mostofsky S, Murray SS, Sowell ER, Bartsch H, Kuperman JM, Brown TT, Hagler DJ Jr, Dale AM, Jernigan TL, St Pourcain B, Davey Smith G, Ring SM, Gruen JR; Pediatric Imaging, Neurocognition, and Genetics Study. Genome-wide association study of shared components of reading disability and language impairment. Genes Brain Behav. 2013 Nov;12(8):792-801. doi: 10.1111/gbb.12085. Epub 2013 Oct 9. PubMed PMID: 24024963; PubMed Central PMCID: PMC3904347. Link to article on publisher's site

Journal/Book/Conference Title

Genes, brain, and behavior

Related Resources

Link to Article in PubMed

PubMed ID

24024963

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

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