Population-based genetic effects for developmental stuttering
Hannah G. Polikowsky,
Douglas M. Shaw,
Lauren E. Petty,
Hung-Hsin Chen,
Dillon G. Pruett,
Jonathon P. Linklater,
Kathryn Z. Viljoen,
Janet M. Beilby,
Heather M. Highland,
Brandt Levitt,
Christy L. Avery,
Kathleen Mullan Harris,
Robin M. Jones,
Jennifer E. Below,
Shelly Jo Kraft
Affiliations
Hannah G. Polikowsky
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA
Douglas M. Shaw
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA
Lauren E. Petty
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA
Hung-Hsin Chen
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA
Dillon G. Pruett
Hearing and Speech Sciences, Vanderbilt University, Nashville, TN, USA
Jonathon P. Linklater
Irish Stammering Association, Dublin, Ireland
Kathryn Z. Viljoen
Curtin School of Allied Health, Curtin University, Perth, WA, Australia
Janet M. Beilby
Curtin School of Allied Health, Curtin University, Perth, WA, Australia
Heather M. Highland
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Brandt Levitt
Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Christy L. Avery
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Kathleen Mullan Harris
Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Robin M. Jones
Hearing and Speech Sciences, Vanderbilt University, Nashville, TN, USA
Jennifer E. Below
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA; Corresponding author
Shelly Jo Kraft
Communication Sciences and Disorders, Wayne State University, Detroit, MI, USA; Corresponding author
Summary: 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.
