trios to show that these mutations are commonly de novo, and associated with more neurodevelopmental and cognitive impairment than cases without such mutations. It is important to note that these rare variant studies do not implicate conclusively any specific gene, but instead reveal an overall (and very modest) excess of such variants in schizophrenia, with clustering to functionally defined gene networks, consistent with the GWAS findings, as described below. Note also that, as with SNPs, proving the causality of a disease-associated rare variant is not a trivial undertaking (MacArthur et al., 2014).
