Genetic and Comorbidity Studies Suggest New Model for Understanding Stuttering

CONFERENCE REPORTER

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Data from genetic and comorbidity studies may provide additional insight into understanding stuttering and developing better treatment strategies, according to a presentation by Shelly Jo Kraft, PhD, MS, at the STARS (Stuttering Treatment and Research Society) Inaugural Education and Research Conference.¹ The conference, held in Dana Point, California, is the first continuing medical education conference dedicated to exploring neurobiology, genetics, and treatment for stuttering.

Shelly Jo Kraft, PhD, MS

Kraft, the director of the Behavior, Speech & Genetics Lab and associate professor of speech language pathology and audiology at Wayne University, suggested the new model is akin to the model used for treating asthma, where the comorbidities associated with the disorder are assessed and addressed as part of the overall patient’s asthma treatment program. For stuttering, that means looking at metabolic and gut issues; attention-deficit/hyperactivity disorder; sleep patterns and disruptions; respiratory disease and asthma patterns; inflammation; and allergies.

Genetics Data

Genomic-wide association studies (GWAS) for stuttering has revealed genes of interest, Kraft told attendees. For instance, ZMAT4 loci reached genome-wide significance for stuttering in individuals with African ancestry, and FAM49A loci is significantly associated with predicted developmental stuttering in individuals with European ancestry.

Of particular interest, she noted, is Ssu-2 Homolog (SSUH2), a protein coding gene. Interestingly, Kraft noted SSUH2 has been associated with muscles that control body movements, including muscle rippling muscle disease (RMD). A rare condition, RMD holds many similarities to stuttering: the condition generally begins in childhood and is characterized by increased muscle irritability. Kraft also said SSUH is expressed in the small and large intestine or what some researchers are calling the “second brain.” Although not much is known about SSUH, she acknowledged that serotonin is involved with the gut and gut microbiome, and it may lead to the connections and comorbidities often seen in individuals who stutter.

Comorbidity Data

Along with colleagues, Kraft conducted a large scale GWAS analyses of stuttering, which was recently published in Nature Genetics.² Their analysis of the genome-wide association study was based on nearly 100,000 cases and more than 1 million controls, and is the largest genetic study of self-reported stuttering to date. Kraft and colleagues found 57 distinct genomic regions and 48 genes associated with stuttering. The data further shared genetic risk profiles that were linked to ADHD, anxiety, asthma, depression, dermatitis, sleep and other comorbidities.

To validate what the genetic studies were showing, Kraft and colleagues developed the Other Health Inventory for Individuals who Stutter (OHI). Individuals were invited to scan a QR code that led them to a questionnaire set up similar to ICD codes. Participants were not required to have formal diagnosis to denote symptoms. Preliminary data indicated gastrointestinal, dermatology, respiratory, sleep, and viral infections, as areas of interest.

A New Biological Understanding

Armed with this and other research, Kraft believes it is time to work toward the development of an endophenotype or intermediate phenotype. Kraft defined endophenotype as a “quantitative biological trait that is reliable in reflecting the function of a discrete biological system and is reasonably heritable, and as such is more closely related to te root cause of the disease than the broad clinical phenotype.”

Such an approach will allow the field and the interdisciplinary treatment team to improve identification and support of individuals who stutter, she said.

To move the needle, Kraft told attendees, “We need to include screening, assessment, and treatment recommendations for comorbid conditions in stuttering populations.” attendees.

Learn more from the STARS Inaugural Education and Research Conference.

References

1. Kraft SJ. Stuttering Genetic Co-Morbidities. Presented at STARS Inaugural Education and Research Conference; Dana Point, California; September 13, 2025.

2. Polikowsky HG, Scartozzi AC, Shaw DM et al. Large-scale genome-wide analyses of stuttering. Nat Genet. 2025;57:1835–1847.