Both COS probands and SIBs showed significant differences from HCs in the relationship between Val dose and CT change. In contrast to HCs (where CT loss was slower with increasing Val dose) within both COS probands and SIBs, greater Val dose was associated with accelerated CT loss. These significant group-by-gene-by-age interactions were most marked between HCs and COS probands within left dlPFC and bilateral cingulate (Fig. 2, co-ordinates for peak vertices in each region are provided in Supplementary Table 2), and between HCs and SIBs within left intraparietal sulcus (IPS) bilateral inferior frontal gyrus (IFG), anterior cingulate and lateral temporal regions (Fig 3, coordinates for peak vertices in each region are provided in Supplementary Table 2). A direct comparison between COS probands and their SIBs, highlighted that significant disruptions of the normative relationship between Val dose and CT in anterior cingulate, lateral temporal and IPS regions where were only seen in unaffected SIBs, and not in COS probands (Supplementary Figure 2).
