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Population-based genetic effects for developmental stuttering.
- Source :
-
HGG advances [HGG Adv] 2021 Dec 02; Vol. 3 (1), pp. 100073. Date of Electronic Publication: 2021 Dec 02 (Print Publication: 2022). - Publication Year :
- 2021
-
Abstract
- Despite a lifetime prevalence of at least 5%, developmental stuttering, characterized by prolongations, blocks, and repetitions of speech sounds, remains a largely idiopathic speech disorder. Family, twin, and segregation studies overwhelmingly support a strong genetic influence on stuttering risk; however, its complex mode of inheritance combined with thus-far underpowered genetic studies contribute to the challenge of identifying and reproducing genes implicated in developmental stuttering susceptibility. We conducted a trans-ancestry genome-wide association study (GWAS) and meta-analysis of developmental stuttering in two primary datasets: The International Stuttering Project comprising 1,345 clinically ascertained cases from multiple global sites and 6,759 matched population controls from the biobank at Vanderbilt University Medical Center (VUMC), and 785 self-reported stuttering cases and 7,572 controls ascertained from The National Longitudinal Study of Adolescent to Adult Health (Add Health). Meta-analysis of these genome-wide association studies identified a genome-wide significant (GWS) signal for clinically reported developmental stuttering in the general population: a protective variant in the intronic or genic upstream region of SSUH2 (rs113284510, protective allele frequency = 7.49%, Z = -5.576, p = 2.46 × 10 <superscript>-8</superscript> ) that acts as an expression quantitative trait locus (eQTL) in esophagus-muscularis tissue by reducing its gene expression. In addition, we identified 15 loci reaching suggestive significance (p < 5 × 10 <superscript>-6</superscript> ). This foundational population-based genetic study of a common speech disorder reports the findings of a clinically ascertained study of developmental stuttering and highlights the need for further research.<br />Competing Interests: The authors declare no competing interests.<br /> (© 2021 The Authors.)
Details
- Language :
- English
- ISSN :
- 2666-2477
- Volume :
- 3
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- HGG advances
- Publication Type :
- Academic Journal
- Accession number :
- 35047858
- Full Text :
- https://doi.org/10.1016/j.xhgg.2021.100073