The strong replication of findings at 16p11.2 also highlights emerging opportunities for translational neuroscience. Firstly, the region is sufficiently circumscribed to interrogate using molecular biological and model systems. Secondly, though we cannot quantify an odds ratio from our data, given the absence of events in siblings, there is clear evidence from this and prior studies (McCarthy et al., 2009) that 16p11.2 CNVs carry much larger effects than any common variant contributing to complex common disorders. Thirdly, the 1% allele frequency allows for prospective studies of natural history, neuroimaging, and treatment response, as, for example, in the recently launched Simons Variation in Individuals Project (https://sfari.org/simons-vip). Finally, the entirety of the data now strongly supports a role for both duplications and deletions of 16p11.2 in social disability. Together, these suggest that cross-disciplinary approaches can begin to address the means by which a single locus leads to a range of psychiatric outcomes previously conceptualized as distinct and to address the critical role that dosage sensitivity plays in the unfolding of these neuro-developmental phenotypes.
