Stuttering is a developmental speech disorder that has one of the highest familial recurrence rates among communication disorders with complex inheritance. Persistent developmental stuttering affects 1% of the adult population, and 5-6% of the child population world-wide with an increased prevalence recently reported in Australia at 11-14%. To date, the genes responsible for the disorder have yet to be identified in the non-consanguineous general population. Only a small number of studies have been conducted on the genetic susceptibility of this disorder, each focusing on families from genetic isolates (Pakistani, African or Hutterite) with high levels of consanguinity. While these are viable approaches utilizing linkage designs, the genome-wide association case-control design offers a promising alternative that is powered to detect common variants of modest to large effects found in general populations that may have an additive or interacting effect on risk of the complex disorder of interest. This proposed study will examine genome-wide genetic risk in 800 unrelated non-consanguineous individuals who stutter and 3000 ancestry matched controls with replication of top signals in an additional independent 1000 cases and 1000 controls, comprising the largest proposed genetic study of stuttering to date and aimed at the identification of genes and transmission models responsible for the disorder.
This study lays the groundwork for the identification of genes contributing to developmental stuttering by analyzing the DNA of 800 affected individuals and 3000 matched controls for genetic variants. Replication of findings will be conducted with 1000 participants who stutter from the BioVU DNA biobank at Vanderbilt University. Top findings will be annotated for tissue specific gene expression using PrediXcan. This approach will provide an unprecedented focus on the role of common genetic variants contributing to stuttering risk in disrupting gene function in people who stutter to provide a more complete understanding of the full genetic architecture of developmental stuttering and the fundamental how and why of the disorder itself.