Discovery of 36 loci significantly associated with stuttering Article Swipe
Jennifer E. Below
,
Hannah G. Polikowsky
,
Alyssa Scartozzi
,
Douglas M. Shaw
,
Dillon G. Pruett
,
Hung‐Hsin Chen
,
Lauren E. Petty
,
Alexander S Petty
,
Emily Lowther
,
Yao Yu
,
Heather M. Highland
,
Christy L. Avery
,
Kathleen Mullan Harris
,
Reyna L. Gordon
,
Janet Beilby
,
Kathy Viljoen
,
Robin M. Jones
,
Chad Huff
,
Shelly Jo Kraft
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-2799926/v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-2799926/v1
Developmental stuttering is a common speech disorder (studies estimate at least a 5% lifetime prevalence) characterized by prolongations, blocks, and repetitions of speech sounds. In approximately 75–80% of cases in early childhood, stuttering will resolve within a few years (referred to as ‘recovery’); the remaining cases will often experience stuttering into school-age years and adulthood (referred to as ‘persistence’). In adults, the prevalence of stuttering is substantially higher in men compared to women, at a ratio of 4:1 or greater (compared to between 1:1 and 2:1 in young children); this has typically been explained by differences in likelihood of recovery by sex. Heritability studies have established that a genetic component for stuttering exists, with heritability estimates as high as 84%. However, genetic factors impacting stuttering risk remain largely uncharacterized. To date, only two prior genome-wide association studies (GWAS) of developmental stuttering have been published, both of which included less than 10,000 cases. Here, we performed eight self-reported stuttering GWAS that were stratified by sex and ancestries. These analyses included more than 1 million individuals (99,776 cases and 1,023,243 controls) and identified 36 unique genome-wide significant loci. We validated the self-reported stuttering phenotype using polygenic risk scores from two independent stuttering datasets. We examined genetic correlation of our GWAS results with published GWAS for other previously identified comorbid traits and found strong evidence of correlation with hearing loss, daytime sleepiness, depression, and poorer beat synchronization. We also performed Mendelian randomization analyses which revealed distinct causal relationships in males and females for genetically associated traits. These distinct causal relationships motivate continued research into sex-specific phenotypic differences, with emphasis on recovery status. Additionally, a high proportion of genes impacting stuttering risk were found to be associated with neurological traits from the GWAS catalog, supporting a neurological basis for stuttering. Our findings provide the first well-powered insight into genetic factors underlying stuttering, representing a major step forward in our understanding of this condition.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-2799926/v1
- https://www.researchsquare.com/article/rs-2799926/latest.pdf
- OA Status
- gold
- Cited By
- 10
- References
- 100
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4367041835
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4367041835Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.21203/rs.3.rs-2799926/v1Digital Object Identifier
- Title
-
Discovery of 36 loci significantly associated with stutteringWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-04-26Full publication date if available
- Authors
-
Jennifer E. Below, Hannah G. Polikowsky, Alyssa Scartozzi, Douglas M. Shaw, Dillon G. Pruett, Hung‐Hsin Chen, Lauren E. Petty, Alexander S Petty, Emily Lowther, Yao Yu, Heather M. Highland, Christy L. Avery, Kathleen Mullan Harris, Reyna L. Gordon, Janet Beilby, Kathy Viljoen, Robin M. Jones, Chad Huff, Shelly Jo KraftList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-2799926/v1Publisher landing page
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https://www.researchsquare.com/article/rs-2799926/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.researchsquare.com/article/rs-2799926/latest.pdfDirect OA link when available
- Concepts
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Stuttering, Psychology, Genetics, Biology, Computational biology, Computer science, Developmental psychologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
10Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 7, 2023: 1Per-year citation counts (last 5 years)
- References (count)
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100Number of works referenced by this work
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-
10Other works algorithmically related by OpenAlex
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