Evidence for familial segregation was sought for five rare exonic variants where additional family members were available, but none segregated perfectly or unequivocally with diagnosis (Supplementary Figure 9). Of note however was the identification of the non-synonymous amino-acid variant R37W (rs137948488), first reported68 in a subject with SZ, and seen here in a single case of rMDD. R37 is strictly conserved among orthologues and recent publications, including our own, have demonstrated biological effects of 37W on DISC1 interactions,32, 73 and shown a dominant-negative effect on the sub-cellular distribution of DISC1.44 Five additional family members of the 37W carrier were available for genotyping diagnosed with rMMD, generalised anxiety disorder, bipolar II or no psychiatric diagnosis at the time of assessment. The R37W mutation was present in relatives with rMDD and generalised anxiety disorder, but not in a relative with bipolar II, or any unaffected individual (Figure 3).
