Speech, language and music
Our unique capacities for speech, language, reading and music are fundamental features of what makes us human (1,2). Yet the underlying biological bases of these traits and related disorders remain largely mysterious. In addition, the interactions and associations between these traits and related disorders have only begun to be unraveled. For example, musicality skills contribute to a wide range of speech, language and reading skills (3). Also, there is a higher prevalence of music-related impairments in individuals with speech-, language- and reading-related disorders (4). Lastly, children with a language impairment are more often diagnosed with a speech sound disorder or reading disorder, indicating comorbidity between these disorders (5). A promising way to study the underlying biological bases of language- and music-related traits and disorders is to capture contributions of genetic variation to individual differences in the relevant capacities and to related disorders in so called genome-wide association studies (GWAS). Results from GWAS can be used to study the neurobiological foundations of the traits/disorders, as well as the genetic overlaps between them.
Stuttering is an example of a speech-related disorder that has yet to benefit from large genetics studies. It is a neurodevelopmental disorder characterized by disfluencies in speech, such as blocks, prolongations and repetitions. Stuttering generally starts early in childhood, affecting approximately 8% of children (6). While most children recover naturally or with speech therapy, up to 1% of adults persist in their stuttering (7). DSM-5 adds to the definition of stuttering the criteria that the disturbance in speech causes anxiety about speaking or limitations in effective communication, social participation, or academic or occupational performance. It can therefore have a large impact on the quality of life of adolescents and adults (8,9), and cause social anxiety (10). Stuttering has also been shown to negatively impact relationships, social interactions and education and employment (11). Mental problems can increase and maintain the severity of stuttering, further exacerbating its impact. Stuttering and its impact can vary substantially from one person to another, but also in different situations and life periods (12) Obtaining information about stuttering and how individuals deal with their stuttering in a large population cohort such as Lifelines, with extensive information available about quality of life and mental health, will provide a great resource to further study the impact of this important trait.
The high variability in stuttering creates a need for personalized interventions. Studies have shown that most interventions for stuttering are at least effective for some people who stutter, but also not effective for others (13,14). In the Netherlands, a wide range of therapies from regular to alternative is available for persons who stutter. Some therapies focus on improving the speech and others on improving the psychosocial consequences. Little is known about the effectiveness and experiences with these different forms of therapy. It is a challenge for people who stutter to find a therapy that fits well with the needs of the individual. Obtaining information about therapy use and positive and negative experiences with these therapies in a large dataset such as Lifelines will yield a valuable resource to investigate the effectiveness of the available therapies.
Twin studies already showed a large genetic component in the risk for developing stuttering, with heritability estimates ranging from 40 to 80% (15). However, research on the molecular basis of stuttering is still in its early days, involving mainly linkage and candidate gene studies (15). Two GWASs on stuttering have been published last year, but were limited by relatively small sample size and imprecise phenotype definitions (16,17). Larger samples with extensive phenotype data are therefore essential to further our understanding of this speech disorder. Some of these samples are currently being collected (see www.geneticavanstotteren.nl and www.geneticsofstutteringstudy.org.au/), but more data is required for powerful GWAS studies and to facilitate genetic analyses of stuttering subtypes. Lifelines has the potential to make a significant contribution to the understanding of the genetic risk factors contributing to stuttering.
Music engagement is a fundamental aspect of human nature and an important contributor to our well-being (18). It likely contributes directly to mental health and also through its effect on language skills. Twin studies already indicated that multiple aspects of musicality are moderately heritable (19), indicating that genetic studies can be used to investigate the biological basis of the overlap between speech, language and reading skills (and related disorders) and musicality. Traits such as rhythm skill, singing, pitch perception, music reward and general musicality can be assessed through a limited number of questions. One example of a musicality trait that has been successfully assessed with a single item question and used for a GWAS study is beat synchronization (20). Obtaining information about multiple musicality traits in a large population cohort such as Lifelines, together with information about speech, language and reading-related traits and disorders, promises to make a substantial impact on this highly innovative area of research.
In general, investigations of language- and music-related traits, as well as their associated disorders, have yet to move to larger sample sizes to allow high-powered GWAS, including developmental language disorder (DLD; previously specific language disorder or SLI) (21), synesthesia (22), and multiple aspects of musicality (19). DLD is a common developmental disorder that is characterized by a difficulty with producing and understanding spoken language, and has been estimated to have a prevalence of up to 7% in preschool children (23). Synesthesia is a neurological phenomenon described often as blending of senses, resulting in automatic associations between for example numbers or music with colours, and between a day of the week and a spatial location (24). The prevalence of the most common forms of synesthesia has been estimated at 1-2%. Including questions on these traits in Lifelines will therefore allow future GWAS, a great starting point to investigate neurobiological foundations of and associations between these traits. The proposed questions on DLD and musicality have been validated in previous studies, and will directly allow for a GWAS on these traits. Studies on the genetics of synesthesia so far always validated self-reported synesthesia by looking at the consistency of the associations between e.g. colours and numbers/letters, or colours and musical tones (22,25). Therefore, the question about synesthesia will benefit from validation during a follow-up study in Lifelines or in a separate cohort, before being used for genetic studies on the trait. Still, synesthesia self-report has, to the extend of our knowledge, never been collected in such a large cohort, therefore Lifelines will provide a great resource to investigate the relation between synesthesia self-report and demographic factors and traits.