Population-based genetic effects for developmental stuttering
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 stutteri...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | HGG Advances |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666247721000543 |
| _version_ | 1818460102722584576 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Hannah G. Polikowsky |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T23:24:55Z |
| format | Article |
| id | doaj.art-6cad16b01d3f42dea70ee797b8a6a279 |
| institution | Directory Open Access Journal |
| issn | 2666-2477 |
| language | English |
| last_indexed | 2024-12-14T23:24:55Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | HGG Advances |
| spelling | doaj.art-6cad16b01d3f42dea70ee797b8a6a2792022-12-21T22:43:50ZengElsevierHGG Advances2666-24772022-01-0131100073Population-based genetic effects for developmental stutteringHannah G. Polikowsky0Douglas M. Shaw1Lauren E. Petty2Hung-Hsin Chen3Dillon G. Pruett4Jonathon P. Linklater5Kathryn Z. Viljoen6Janet M. Beilby7Heather M. Highland8Brandt Levitt9Christy L. Avery10Kathleen Mullan Harris11Robin M. Jones12Jennifer E. Below13Shelly Jo Kraft14Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USAVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USAVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USAVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USAHearing and Speech Sciences, Vanderbilt University, Nashville, TN, USAIrish Stammering Association, Dublin, IrelandCurtin School of Allied Health, Curtin University, Perth, WA, AustraliaCurtin School of Allied Health, Curtin University, Perth, WA, AustraliaDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USACarolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADepartment 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, USACarolina 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, USAHearing and Speech Sciences, Vanderbilt University, Nashville, TN, USAVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA; Corresponding authorCommunication Sciences and Disorders, Wayne State University, Detroit, MI, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2666247721000543genome-wide assocation studystutteringpopulation-studycomplex trait |
| spellingShingle | 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 Population-based genetic effects for developmental stuttering HGG Advances genome-wide assocation study stuttering population-study complex trait |
| title | Population-based genetic effects for developmental stuttering |
| title_full | Population-based genetic effects for developmental stuttering |
| title_fullStr | Population-based genetic effects for developmental stuttering |
| title_full_unstemmed | Population-based genetic effects for developmental stuttering |
| title_short | Population-based genetic effects for developmental stuttering |
| title_sort | population based genetic effects for developmental stuttering |
| topic | genome-wide assocation study stuttering population-study complex trait |
| url | http://www.sciencedirect.com/science/article/pii/S2666247721000543 |
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