Autism spectrum disorder (ASD) is diagnosed in roughly 1% of the population [1, 2] and has complex genetic roots. The recurrence risk of developing ASD in siblings of an affected individual is approximately 7–19% [3–5], and estimates of heritability are high from both twin (64−91%) [6] and whole genome genotyping studies (31−71%) [7]. Analysis of rare and de novo structural and sequence variation in ASD has had recent success in identifying genes and the biology underpinning ASD, albeit with direct relevance to only a small proportion of cases. The establishment of a number of robust risk genes such as CHD8, GRIN2B, SCN2A, and SYNGAP1 [8], and gene-set analyses from associated structural variation have identified synaptic functioning, chromatin remodelling, Wnt signalling, transcriptional regulation, fragile X mental retardation protein (FMRP) interactors and, more broadly, MAPK signalling, as putative biological processes that are disrupted in ASD [9–13].
