Poster Presentation GENEMAPPERS 2026

Unravelling the genetic basis of stuttering: results and insights from a GWAS meta-analysis (#68)

Vicki E Jackson 1 2 , Jenna J Shin 1 2 , Sarah Horton 3 4 , Jess O Boyce 3 4 , Sheena Reilly 5 , Olivia van Reyk 4 , Nathan A Gillespie 6 7 , Ingrid E Scheffer 8 9 , David J Amor 9 , Michael S Hildebrand 8 9 , Else Eising 10 , Simon E Fisher 10 11 , Nicholas G Martin 6 , Angela T Morgan 3 4 , Melanie Bahlo 1 2
  1. Genetics and Gene Regulation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia
  3. Department of Audiology and Speech Pathology, University of Melbourne, Parkville, VIC, Australia
  4. Speech and Language, Murdoch Children’s Research Institute, Melbourne, VIC, Australia
  5. Menzies Health Institute Queensland, Griffith University, Southport, QLD, Australia
  6. QIMR Berghofer Medical Research Institute, Bribane, QLD, Australia
  7. Virginia Institute for Psychiatric and Behaviour Genetics, Virginia Commonwealth University, Charlottesville, VA, USA
  8. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC, Australia
  9. Murdoch Children's Research Institute and University of Melbourne Department of Paediatrics, Royal Children's Hospital, Parkville, VIC, Australia
  10. Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands
  11. Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands

Characterised by dysfluent speech, stuttering is a complex communication disorder that profoundly affects an individual's social and mental wellbeing. Up to 11% of children commence stuttering by 4 years of age, with approximately one third developing persistent stuttering. Whilst the exact cause remains unknown, twin- and family-based studies suggest a significant genetic component.

We hypothesised that common genetic variation contributes substantially to stuttering risk. To investigate this, we conducted a large-scale genome-wide association study (GWAS) meta-analysis of stuttering, encompassing data from multiple population-based cohorts and ascertained case collections, including our Genetics of Stuttering (GenStutt) Study, which directly recruited people who stutter from Australia, New Zealand and the UK.

Our primary GWAS meta-analysis focused on ever stuttering (current or previous), including up to 6,096 cases and 82,023 controls from 15 cohorts. We also conducted secondary analyses on persistent stuttering (1,766 cases vs 39,392 controls) and sex-stratified analyses for ever stuttering.

We will present key findings from our comprehensive analyses, including heritability estimates and notable implicated effector genes. We assessed potential sex differences in genetic associations and explored the effect of phenotype heterogeneity through separate analyses of ascertained and general population cohorts. To further investigate stuttering persistence, we employed multi-trait analysis of GWAS (MTAG) and GWAS-by-subtraction approaches. Additionally, we examined the overlap with SNPs and genes implicated in a GWAS of self-reported stuttering in the 23andMe cohort. Our analyses also identified brain regions potentially involved in stuttering aetiology, providing insights into the biological underpinnings of this complex disorder.