Diagnoses of SZ, BP and rMDD were all present in the original Scottish family carrying the translocation that disrupts DISC1. All three DSMIV diagnoses have a strong and overlapping genetic component, but robust statistical analysis of gene-level contributions to risk are complicated by extensive genetic heterogeneity within and between diagnoses.4 We have provided the most comprehensive landscape of genetic variation at the DISC1 locus to date in patients with this spectrum of psychiatric illness and in healthy population controls with quantitative measures of mood and cognition. Comparison between our sequencing study and that of the 1000 Genomes Project confirms that current genome-wide association studies effectively captures the majority of common (but not rare) variants in the European population. Our sample size is large by current sequencing study standards, but we lack power to detect genome-wide significant P-values for either common or rare variants (see Supplementary Information and Supplementary Figure S11 for further details and also Kiezun et al.).74 Indeed, the predicted abundance of independent rare variants at this (and any other given) locus makes it highly improbable that any one
