Genetic And Biological Pathways Underpinning Communication Disorders Across The Lifespan PDF Download

Interpersonal communication is a vital component of everyday life which can be negatively affected by speech sound disorders (SSD). SSD affect articulation and phonological processes, are the most common type of communication disorder, and occur in 16% of three year olds. Despite the frequency with which they occur, SSD are relatively understudied compared to other communication disorders such as dyslexia and specific language impairment. SSD can occur due to craniofacial abnormalities, hearing loss, as a symptom of certain syndromes, or due to unknown causes. SSD of unknown cause are heritable with monozygotic twin concordance rates of 0.95, but the genetic basis is not well defined. Many previous studies have focused upon FOXP2, a gene harboring a causal mutation in one large family, or genes and loci associated with language impairment (LI) or dyslexia (RD), frequently comorbid conditions. The weakness of these approaches is they are self-limiting and cannot identify novel loci. Consequently, it would be beneficial to address the etiology of SSD agnostically to identify novel loci and characterize the genetic architecture of what is likely a multifactorial disorder. To do so, data from the Cleveland Family Speech and Reading Study, a longitudinal study of children with SSD, were used to perform the first known genome-wide association study on traits associated with SSD endophenotypes in a sample ascertained based on speech sound disorder diagnosis. This analysis identified novel loci, replicated previous findings, and informed hypotheses regarding biological pathways that may be involve in SSD. To investigate the impact of LI and RD on genetic association with SSD endophenotypes, the changes in genetic effect estimates after adjusting for the conditions were analyzed. Some effects were unchanged by LI and RD status suggesting a foundational role of these loci in human communication. Finally a pathway analysis revealed similarities between SSD and other neuropathologies such as autism spectrum disorders and Alzheimer's disease. This study represents a thorough examination of the genetic underpinnings of SSD and other communication traits, is the first genome-wide association study for SSD, and supports a multifactorial genetic architecture underlying both typical and atypical communication.