Unravelling the genetic basis of stuttering: GWAS meta-analysis highlights link with rare speech disorders
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Background: Developmental stuttering affects up to 11% of children globally, with around one-fifth developing a persistent lifelong stutter. Twin and family studies indicate a strong genetic contribution and comorbidity with other heritable traits. Despite efforts to investigate the common genetic architecture of stuttering, much of variation contributing to clinically ascertained stuttering, persistence and recovery remains uncharacterised. Methods: We performed a genome-wide association study (GWAS) meta-analysis of stuttering across 18 cohorts (6,096 cases, 81,629 controls) of European ancestries, with secondary analyses of stuttering persistence and sex-stratified GWAS. Findings: . A polygenic risk score derived from this independent GWAS was associated with stuttering susceptibility and severity within clinically ascertained cases. Partitioned heritability analysis pointed to enrichment in conserved regulatory regions, and integration with imaging data highlighted motor circuitry including decreased pallidum volume and cerebellar and white-matter microstructural differences. Interpretation: Our findings support common variant associations in stuttering converging on genes implicated in speech and neurodevelopmental conditions, pointing to basal ganglia-cerebellar motor circuits as central to speech motor control. Funding: Australian National Health and Medical Research Council. Research in context: Our findings suggest that common genetic variation contributing to stuttering converges on the same genes and brain circuits implicated in rare, severe speech disorders. This strengthens the case that stuttering, at least in part, shares a biological basis with other neurodevelopmental and speech-motor conditions, and points to the basal ganglia- cerebellar motor circuit as a promising target for future mechanistic research. For clinicians and people who stutter, these findings do not yet have direct treatment implications, but they lay groundwork for better understanding why stuttering persists in some individuals and not others, and highlight the value of collecting detailed speech and language phenotypes in future large-scale genetic studies.
Source: medRxiv
Authors: Victoria E. Jackson, Jenna J. Shin, Sarah Horton, Jessica O. Boyce, Else Eising, Olivia van Reyk, Richard Parker, Daisy G.Y. Thompson-Lake, Meghan Evans, Janet Beilby, Jennifer E. Below, Dorret I. Boomsma, Elinor Bridges, Elizabeth C. Corfield, Marie-Christine J. Franken, Scott D. Gordon, Alexandra Havdahl, Simone P.C. Koenraads, Shelly Jo Kraft, Michelle Luciano, Gunn-Helen Moen, Hayley S. Mountford, Agnieszka Musial, Craig E. Pennell, Hannah G. Polikowsky, René Pool, Valerie A. Rebattu, Kaili Rimfeld, Alyssa C. Scartozzi, Beate St Pourcain, Ingrid A. Szilagyi, Stian B. Valand, Kathryn Z. Viljoen, Carol A. Wang, Andrew J.O. Whitehouse, Yvonne E. Wren, Elsje van Bergen, Nathan A. Gillespie, Adam P. Vogel, Ingrid E. Scheffer, Michael S. Hildebrand, Lynette G. Sadleir, Frédérique Liégeois, Sheena Reilly, Simon E. Fisher, Nicholas G. Martin, Angela T. Morgan, Melanie Bahlo
Institutions: The University of Melbourne, Walter and Eliza Hall Institute of Medical Research, Murdoch Children's Research Institute, Max Planck Institute for Psycholinguistics, QIMR Berghofer Medical Research Institute, University College London, University of Virginia, University of Otago, Curtin University, Vanderbilt University Medical Center, Amsterdam Neuroscience, Amsterdam Public Health, Amsterdam Reproduction Development, Vrije Universiteit Amsterdam, University of Edinburgh, Norwegian Institute of Public Health, University of Bristol, Lovisenberg Diakonale Sykehus, MRC Integrative Epidemiology Unit, Erasmus MC, University of Oslo, Wayne State University, The University of Queensland, Institute for Molecular Bioscience, Queen Mary University of London, Hunter Medical Research Institute, University of Newcastle Australia, Leiden University Medical Center, University of London, King's College London, Royal Holloway University of London, Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, The Kids Research Institute Australia, The University of Western Australia, North Bristol NHS Trust, Cardiff Metropolitan University, Karolinska Institutet, Virginia Commonwealth University, Royal Children's Hospital, Austin Health, Griffith University
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: green
Funders: Foundation for the National Institutes of Health, Wayne State University, Wellcome Trust, Scottish Government, Vanderbilt University Medical Center, Government of the United Kingdom, UK Research and Innovation, Australian Government, Trond Mohn stiftelse, Scottish Funding Council, European Commission, University of Bristol, Rijksuniversiteit Groningen, Radboud Universiteit, Ministerie van Volksgezondheid, Welzijn en Sport, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Max-Planck-Gesellschaft, Universitetet i Bergen, Universitair Medisch Centrum Groningen, Universitetet i Oslo, Norges Forskningsråd, Russian Science Foundation, Novo Nordisk Fonden, National Institutes of Health, Directorate for Biological Sciences, HORIZON EUROPE Framework Programme, Canadian Institutes of Health Research, Medical Research Council, Economic and Social Research Council, National Health and Medical Research Council, Helse Sør-Øst RHF, Staatssekretariat für Bildung, Forschung und Innovation, Norwegian Institute of Public Health, National Institute of Mental Health, National Institute on Deafness and Other Communication Disorders
Awards: G1028663679, G1037925530, G1093531541, G126399678, G1274085498, G1317305699, G1365939530, G1545006349, Centre for Research Excellence in Speech and Language Neurobiology (CRE-SLANG), G1579503467, G1855934557, G1997327697, Centre for Longitudinal Studies, Resource Centre 2015-20, G2084304408, G2187532201, G2230720350, G240382578, G2437620908, Molecular biology of frontotemporal dementia, Understanding genetic and environmental causes of chronic adult disease in early life, G2572253437, G259633682, The Avon Longitudinal Study of Parents and Children (ALSPAC) 2024-2029, G2861369480, G286142948, G2891576335, G294002421, G2985766253, BBMRI-NL2.0: The NL-Biobank Research Facility, G3123452890, THE CYCLE OF OBESITY: Two generations of a pregnancy cohort to investigate obesity epigenetics, Generation Scotland:NextGenScot, G3175323542, G3297564153, G3444887196, Childhood Risk Factors for Adult Heart Disease, Obesity and Diabetes - 16 year follow up of a Longitudinal Study, G357049385, Generation Scotland:NextGenScot, Risk and Resilience in Developmental Diversity and Mental Health, Genomics of Developmental Trajectories in Twins, G4150868890, Stratifying Resilience and Depression Longitudinally (STRADL), G4319942217, G4374337615, G4411843255, G4460629988, Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strateg, G452649895, G4552237235, G4663226093, Genetic Study of Developmental Stuttering., G5277938394, G536866722, G5388449085, Developmental stuttering: Population-based genetic discovery, G5661816168, G5732418131, G5772921230, Mendelian Randomisation, G5972361449, G6144234142, Stratifying Resilience and Depression Longitudinally (STRADL), Psychophysiology of Childhood Stuttering: Cognitive-Emotional Mechanisms, G6659087414, G6663973959, 58FORWARDS. (The 1958 Birth Cohort: Fostering new Opportunities for Research via Wider Access to Reliable Data and Samples)., G7051064115, G7065913981, G7168425557, G7376853501, G7405370422, G7410593143, Netherlands Twin Registry Repository: researching the interplay between genome and environment, G7655969080, G7689853932, G7759330297, Genetics, educational environments, and student mental health: causal links and long-term outcomes, Integration of Genomics & Transcriptomics in Normal Twins & Major Depression, Finding the first genomic loci for stuttering, G8180280471, G8383967617, G84497985, Genetics of speech disorders: improving diagnosis, prognosis and management, G8662178672, G8683901919, G86865590, G8724570043, G8745459150, G8776062500, Biology of speech disorders: advancing diagnosis, prognosis & management, G9000126205, G9000192955, G9000212799, Functional characterizations of the genetic etiology of stuttering, Early childhood stuttering and risk for persistence: The impact of emotion on speech and cognitive control
OpenAlex ID: W7213457047