Population-Based Genetic Effects for Developmental Stuttering

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Citation

Polikowsky, Hannah G.; Shaw, Douglas M.; Petty, Lauren E.; Chen, Hung-Hsin; Pruett, Dillon G.; Linklater, Jonathon P.; Viljoen, Kathryn Z.; Beilby, Janet M.; Highland, Heather M.; & Levitt, Brandt, et al. (2021). Population-Based Genetic Effects for Developmental Stuttering. HGG Advances, 3(1), 100073. PMCID: PMC8756529

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(-8)) 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(-6)). 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.

URL

http://dx.doi.org/10.1016/j.xhgg.2021.100073

Reference Type

Journal Article

Year Published

2021

Journal Title

HGG Advances

Author(s)

Polikowsky, Hannah G.
Shaw, Douglas M.
Petty, Lauren E.
Chen, Hung-Hsin
Pruett, Dillon G.
Linklater, Jonathon P.
Viljoen, Kathryn Z.
Beilby, Janet M.
Highland, Heather M.
Levitt, Brandt
Avery, Christy L.
Mullan Harris, Kathleen
Jones, Robin M.
Below, Jennifer E.
Kraft, Shelly Jo

Article Type

Regular

PMCID

PMC8756529

Data Set/Study

National Longitudinal Study of Adolescent to Adult Health (Add Health)
Vanderbilt University Medical Center (VUMC) Biobank
International Stuttering Project

ORCiD

Harris, KM - 0000-0001-9757-1026
Avery - 0000-0002-1044-8162