Genome-wide association studies of SZ, BP and rMDD are most consistent with a polygenic liability for common variants, but they also imply that there is real ‘missing' genetic variation, which is most likely due to risk variants having low frequency in the population. To test for evidence of DISC1 association, we applied the Fisher's exact test across all variants and all diagnoses (Figure 2). There was no evidence for SNP association at genome-wide levels of significance for any diagnosis when considered separately or combined, nor was there evidence for locus-wide association of variants with SZ or BP. We did detect a novel, locus-wide empirical association P=0.026 (OR=3.48, 95% CI=1.95–6.23, unadjusted P=6.3 × 10−5) between intronic variant rs16856199 and rMDD. We speculated that individual risk alleles might be predicted to segregate with disease in families. Twelve additional family members were available for genotyping for four rs16856199 carriers. The rs16856199 risk allele segregated with rMDD in all four families (Supplementary Figure S4).
