Unravelling the genetic basis of stuttering: GWAS meta-analysis highlights link with rare speech disorders

@misc{jackson2026unravelling,
  title = {{Unravelling the genetic basis of stuttering: GWAS meta-analysis highlights link with rare speech disorders}},
  author = {V. E. Jackson and J. J. Shin and S. Horton and J. O. Boyce and E. Eising and O. van Reyk and R. Parker and D. G. Y. Thompson-Lake and M. Evans and J. Beilby and J. E. Below and D. I. Boomsma and E. Bridges and E. C. Corfield and M.-C. J. Franken and S. D. Gordon and A. Havdahl and S. P. C. Koenraads and S. J. Kraft and M. Luciano and G.-H. Moen and H. S. Mountford and A. Musial and C. E. Pennell and H. G. Polikowsky and R. Pool and V. A. Rebattu and K. Rimfeld and A. C. Scartozzi and B. St Pourcain and I. A. Szilagyi and S. B. Valand and K. Z. Viljoen and C. A. Wang and A. J. O. Whitehouse and Y. E. Wren and E. van Bergen and N. A. Gillespie and A. P. Vogel and Scheffer},
  howpublished = {medRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.15.26363183},
  url = {https://www.medrxiv.org/content/10.64898/2026.09.15.26363183v1},
  note = {CC BY-NC-ND},
}

TY  - UNPB
TI  - Unravelling the genetic basis of stuttering: GWAS meta-analysis highlights link with rare speech disorders
AU  - V. E. Jackson
AU  - J. J. Shin
AU  - S. Horton
AU  - J. O. Boyce
AU  - E. Eising
AU  - O. van Reyk
AU  - R. Parker
AU  - D. G. Y. Thompson-Lake
AU  - M. Evans
AU  - J. Beilby
AU  - J. E. Below
AU  - D. I. Boomsma
AU  - E. Bridges
AU  - E. C. Corfield
AU  - M.-C. J. Franken
AU  - S. D. Gordon
AU  - A. Havdahl
AU  - S. P. C. Koenraads
AU  - S. J. Kraft
AU  - M. Luciano
AU  - G.-H. Moen
AU  - H. S. Mountford
AU  - A. Musial
AU  - C. E. Pennell
AU  - H. G. Polikowsky
AU  - R. Pool
AU  - V. A. Rebattu
AU  - K. Rimfeld
AU  - A. C. Scartozzi
AU  - B. St Pourcain
AU  - I. A. Szilagyi
AU  - S. B. Valand
AU  - K. Z. Viljoen
AU  - C. A. Wang
AU  - A. J. O. Whitehouse
AU  - Y. E. Wren
AU  - E. van Bergen
AU  - N. A. Gillespie
AU  - A. P. Vogel
AU  - Scheffer
PY  - 2026
DA  - 2026/09/15
PB  - medRxiv
DO  - 10.64898/2026.09.15.26363183
UR  - https://www.medrxiv.org/content/10.64898/2026.09.15.26363183v1
AB  - Developmental stuttering affects up to 11% of children, with around one-fifth developing a persistent stutter. Twin and family studies indicate a strong genetic contribution and comorbidity with other heritable traits, but the common genetic architecture of clinically ascertained stuttering, persistence and recovery remains poorly characterised. We performed a genome-wide association study (GWAS) meta-analysis of 6,096 cases and 81,629 controls of European ancestries from 18 cohorts, including 2,953 cases from stuttering-specific collections with clinically confirmed or validated self-reported phenotypes. We additionally analysed persistence, severity and frequency, and integrated our results with an independent GWAS of self-reported stuttering. Our meta-analysis and the self-report GWAS showed high genetic correlation (rg = 0.66). A polygenic score from the self-report GWAS was associated with stuttering in our ascertained cases, with modest predictive value ({Delta}AUC = 0.067, p = 1.8 x 10-23), and with greater severity and frequency among people who stutter. We replicated two self-report loci (CAMTA1, CTNND2), and combined analysis identified a genome-wide significant association at MPPED2. Our 24 suggestive loci implicated genes with established roles in childhood apraxia of speech, including SETBP1, CAMTA1, PTBP2, GRIN2A and KIRREL3, with strong enrichment for apraxia genes (OR = 40.1, p = 1 x 10-4). Within our meta-analysis, persistent stuttering was genetically near-identical to stuttering overall (rg = 0.97). Genetically predicted brain imaging nominally implicated basal ganglia and cerebellar motor circuitry. Common-variant liability to stuttering is shared across ascertainment approaches, relates to severity, and converges with rare-variant genes for speech disorders on circuits underlying speech motor control.
ER  -