An analytical framework for whole-genome sequence association studies and its implications for autism spectrum disorder

Joon-Yong An

School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul, Republic of Korea

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a strong genetic component. Recently developed genomic technologies, including microarray and next-generation sequencing (NGS), have enabled researchers to genetic analyses aimed at identifying genetic variations associated with ASD and to elucidate the genetic architecture of the disorder. In particular, whole genome sequencing (WGS) has enabled the identification of de novo or rare noncoding mutations that have been unexplored in earlier WES studies and the comparison between the risk associated with coding and noncoding mutations with respect to human disorders and traits. In this presentation, I will introduce the latest finding of large-scale WES and WGS studies of ASD. Analyzing a high-depth WGS dataset of ~2,000 families, including individuals diagnosed for ASD, revealed the phenotypic spectrum and distinct genetic architecture for coding and noncoding variants. We applied de novo risk scores to stratify noncoding risk associated with ASD. Integrating previous ASD-WGS studies, we further highlighted cellular specificity in female and male-risk genes in early neurodevelopment. We then described a unique genetic component enriched for comorbid conditions in multiplex families, putatively providing a novel insight into ASD families.