derived information used to optimise the quality control filters. After quality control screening, all exonic and low frequency (MAF<1%) variants were also validated by Sanger chemistry sequencing as above. The variants were functionally annotated using SNPnexus50 (http://www.snp-nexus.org). Non-coding variants were annotated using the UCSC table browser for the following tracks: ‘RepeatMasker',51 ‘CpG island', ‘TFBS conserved', ‘7x Reg Potential' (which substantially overlaps with DNAse hypersensitivity sites) and/or ‘28-Way Most conserved—PlacMammal' (http://genome.ucsc.edu/). Sequence variants classified as coding were mapped to the DISC1 L isoform and potential pathogenicity ascribed using Pmut,52 Panther53 and PolyPhen-2.54 The coding sequence variants were mapped onto a list of known curated DISC1-interactor binding sites31 and with other functional elements (for example, phosphorylation sites55). Case–control association was tested on the combined case samples as well as individually for SZ, BP and rMDD using Fisher's exact test. Permutation was used to derive region-wide P-values and significance thresholds. Quantitative trait association analyses using LBC1936 samples were performed by linear regression of the trait residuals (adjusted for age and sex) on the number of minor alleles at each SNP, with empirical P-values estimated by permutation to avoid issues with the test statistic distribution caused by the combination of rare variants and slight
