To explore the burden of SNPs of potential functional significance, all variants with MAF <1% were first validated by ABI3730 sequencing. There was no significant overall difference in the number of singleton variants (Supplementary Figure S10) or in the overall number of minor alleles by diagnosis (see Supplementary Methods). SNPs were classified on the basis of bioinformatic annotation into seven functional classes: those in exons including untranslated exons, coding sequence, non-synonymous coding SNPs, conserved regions, regions with regulatory potential, conserved transcription factor binding sites and CpG islands (see Materials and methods and Supplementary Table S7). The empirical P-values for the burden analysis were obtained by permutation correcting for the multiple thresholds tested, but not for the multiple functional subgroups or diagnostic classes (SZ, BP and rMDD and all cases combined), therefore all results are reported as nominal significance values (Supplementary Table S8; Supplementary Methods). Details of nominally significant results are given in Table 1. For rMDD only, there was a nominally significant (P=0.044) excess of minor alleles for SNPs with regulatory potential across all frequencies, and for rare SNPs in
