Five variants were only observed in affected individuals from our study (R37W, A83V, W160L, R233K and R418H), but not in 889 control individuals. Four of these non-synonymous case-only singletons are located in the largest coding exon, DISC1 exon 2, and the remaining variant is in DISC1 exon 4 (Figure 1). A83V was seen in a single individual with BD; this variant is predicted to be deleterious by PolyPhen-2 and Pmut and has been shown to affect wnt signalling.41 It was however observed at low frequency in controls and in individuals with partial agenesis of the corpus callosum in previous studies (Supplementary Table S3).11, 14, 16 Apart from R37W and A83V, none of the three remaining non-synonymous variants, W160L, R233K and R418H, are consistently predicted by the three prediction algorithms to have functional effects (Supplementary Table S2). 160L and 418H were detected in single SCZ individuals and have also previously been reported in individuals with SCZ; but 160L has also been detected in control individuals.10 The variant 233K has not been previously reported, and was identified in an individual with rMDD.
