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Population-based genetic effects for developmental stuttering.

Hannah G Polikowsky1, Douglas M Shaw1, Lauren E Petty1

  • 1Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.

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|January 20, 2022
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Summary
This summary is machine-generated.

Genetic research on developmental stuttering identified a protective variant in the SSUH2 gene. This finding advances our understanding of the genetic underpinnings of this common speech disorder.

Keywords:
complex traitgenome-wide assocation studypopulation-studystuttering

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Area of Science:

  • Genetics
  • Speech and Language Disorders
  • Human Genomics

Background:

  • Developmental stuttering is a common speech disorder with a significant genetic component, yet its inheritance is complex and poorly understood.
  • Previous genetic studies have been underpowered, hindering the identification of specific genes contributing to stuttering susceptibility.
  • Understanding the genetic basis of stuttering is crucial for developing targeted interventions.

Purpose of the Study:

  • To conduct a trans-ancestry genome-wide association study (GWAS) and meta-analysis to identify genetic variants associated with developmental stuttering.
  • To investigate the genetic architecture of stuttering in large, diverse populations.
  • To pinpoint specific genes and pathways involved in stuttering risk.

Main Methods:

  • Meta-analysis of two large datasets: The International Stuttering Project (1,345 cases, 6,759 controls) and The National Longitudinal Study of Adolescent to Adult Health (Add Health) (785 cases, 7,572 controls).
  • Genome-wide association study (GWAS) analysis across diverse ancestries.
  • Expression quantitative trait locus (eQTL) analysis to assess the functional impact of identified variants.

Main Results:

  • Identified a genome-wide significant protective variant (rs113284510) in the SSUH2 gene associated with developmental stuttering.
  • The protective variant acts as an expression quantitative trait locus (eQTL), reducing SSUH2 gene expression in esophagus-muscularis tissue.
  • Discovered 15 additional loci with suggestive significance (p < 5 × 10⁻⁶), indicating potential novel genetic associations.

Conclusions:

  • This study provides foundational population-based genetic insights into developmental stuttering.
  • The identification of a protective variant in SSUH2 highlights its potential role in stuttering etiology.
  • Further research is needed to elucidate the complex genetic factors contributing to stuttering susceptibility and to validate additional identified loci.