Association between genes regulating neural pathways for quantitative traits of speech and language disorders

Penelope Benchek, Robert P Igo Jr., Heather Voss-Hoynes, Yvonne E Wren, Gabrielle Miller, Barbara Truitt, Wen Zhang, Michael Osterman, Lisa Freebairn, Jessica Tag, Gerry Taylor, E. Ricky Chan, Panos Roussos, Barbara Lewis, Catherine Stein*, Sudha Iyengar*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

5 Citations (Scopus)
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Speech sound disorders (SSD) manifest as difficulties in phonological memory and awareness, oral motor function, language, vocabulary, reading and spelling. Families enriched for SSD are rare, and typically display a cluster of deficits. We conducted a genome-wide association study (GWAS) in 435 children from 148 families in the Cleveland Family Speech and Reading study (CFSRS), examining 16 variables representing 6 domains. Replication was conducted using the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 18 significant loci (combined p<10-8) that we pursued bioinformatically. We prioritized 5 novel gene regions with likely functional repercussions on neural pathways, including those which colocalized with differentially methylated regions in our sample. Polygenic risk scores for receptive language, expressive vocabulary, phonological awareness, phonological memory, spelling, and reading decoding associated with increasing clinical severity. In summary, neural genetic influence on SSD is primarily multigenic and acts on genomic regulatory elements, similar to other neurodevelopmental disorders.
Original languageEnglish
Article number64
Number of pages11
JournalNPJ Genomic Medicine
Issue number1
Early online date27 Jul 2021
Publication statusE-pub ahead of print - 27 Jul 2021

Bibliographical note

Funding Information:
We would like to thank the families who have so generously participated in this study for many years. This research was supported by the Genomics Core Facility of the CWRU School of Medicine’s Genetics and Genome Sciences Department. This work made use of the High-Performance Computing Resource in the Core Facility for Advanced Research Computing at Case Western Reserve University. This work was supported by NIH grant R01DC000528 awarded to Dr. Lewis and R01DC012380 awarded to Dr. Iyengar. We are extremely grateful to all the families who took part in the ALSPAC study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and Dr. Sudha Iyengar will serve as guarantor for the contents of this paper. GWAS data for ALSPAC was generated at the Genotyping Facilities at Wellcome Sanger Institute.

Publisher Copyright:
© 2021, The Author(s).


  • Psychiatric disorders
  • Genome-wide association studies


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