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

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 (r _g = 0.66). A polygenic score from the self-report GWAS was associated with stuttering in our ascertained cases, with modest predictive value (ΔAUC = 0.067, p = 1.8 × 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 × 10⁻⁴). Within our meta-analysis, persistent stuttering was genetically near-identical to stuttering overall (r _g = 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.