Genomic Investigations of Spoken and Written Language Abilities: A Guide to Advances in Approaches, Technologies, and Discovery

Purpose: The aim of this tutorial is to show how the rise of molecular technologies and analytical methods in human genetics yields exciting new ways to understand the biological foundations of spoken and written language. The focus is on complementary strategies capturing genetic variation of different kinds (rare gene disruptions and common DNA polymorphisms), discussing how these can be associated with developmental speech, language, and reading disorders as well as with interindividual differences in the general population. Results: The first half of the tutorial discusses rare variants that are sufficient themselves to cause a severe speech and/or language disorder. This begins with lessons learned from studying FOXP2 disruptions that cause childhood apraxia of speech, accompanied by impaired language production and comprehension, before considering how genome or exome sequencing has uncovered pathogenic variants in an array of additional neurodevelopmental genes, including CHD3 , DDX3X , KAT6A , SETBP1 , SETD1A , WDR5 , and ZFHX4 . The second half of the tutorial covers the study of common DNA variants with individually tiny effect sizes, highlighting the challenges of robustly associating them with variability in language-related skills. Against this background, a shift from small candidate gene studies to large-scale genome-wide association study designs is transforming the landscape of the field, gaining leverage from team science approaches and personal genomics. The shift is illustrated with selected examples of recent studies of relevant quantitative measures and diagnostic status in many thousands of participants. Conclusions: This work demonstrates the dramatic impact genomic innovations are having on the language sciences and how molecular genetic approaches can address long-standing questions about neurobiology and the evolution of distinctive human traits. Potential translational consequences for speech or language pathology vary according to the types of DNA variation and will benefit from enhanced communication about the roles of genomics in clinical contexts.