Leveraging gene discovery to illuminate neurodevelopment pathophysiology: opportunities and challenges in Autism Spectrum Disorders

Abstract: The last several years has ushered in a new age in psychiatric genetics and genomics. The maturation of analytic strategies and genomic technologies, combined with a more nuanced understanding of the varied genetic architectures of different psychiatric disorders, has led to highly replicable results, including for autism spectrum disorder (ASD) This has transformed the literature from a preoccupation with the identification of candidate genes to the discovery of bona fide, reproducible risk mutations and alleles. The challenge for the field now is harnessing these molecular clues to reveal an actionable understanding of pathophysiology. The lecture will review recent discoveries emerging from studies of rare de novo variation in ASD. It will describe several alternative strategies for interpreting these findings and will address both the progress and challenges that are associated with these efforts.