Rare disruptive variants in the DISC1 Interactome and Regulome: association with cognitive ability and schizophrenia

Figure 1. Gene set burden analysis of rare functional variants for case-control traits. Case-control gene set burden analysis of singletons and rare variants (MAF<1%) in the DISC1 Interactome (left) and Regulome (right). x-axis represents –log10(P), vertical dashed line: P=0.05, vertical solid line: FWERacross P=0.05; Odds ratio (OR) is labeled for the significant tests with P<0.05. Disruptive mutations, which included nonsense and splice site variants; NSstrict, Non-synonymous strict damaging mutations which included disruptive variants plus missense variants predicted as damaging by all five algorithms (PolyPhen2 HumDiv and HumVar, SIFT, LRT and MutationTaster); NSbroad, Non-synonymous broad damaging mutations which included disruptive plus missense variants predicted as damaging by at least one of the algorithms above.

Figure 2. Translin-associated factor X interacting protein 1 (TSNAXIP1) rare functional variants. TSNAXIP1 exon structure and mutations. Definitions of Disruptive (red), NSstrict (underlined) and NSbroad mutations are given in Figure 1. Neutral variants (green) were defined as missense variants predicted as not damaging by any of the five predictive algorithms. Dash lines represent the variants present in the European subset of the 1000 Genomes Project (1000G_EU), and the solid lines represent the variants present in the 1000G_EU. The number of circles represents the number of samples carry the rare variant.

Figure 3. Gene set burden analysis of rare functional variants for quantitative traits. Quantitative trait gene set burden analysis of singletons and rare variants (MAF<1%) in the DISC1 Interactome (left) and Regulome (right). x-axis represents –log10(P), vertical dashed line: P=0.05, vertical solid line: FWERacross P=0.05; Effect size (β, Beta) is labeled for the significant tests with P<0.05. See phenotype descriptions in Supplementary Information for all quantitative traits. Moray House Test is the mental ability test used in the LBC1936 cohort. A priori hypothesis is that an increased burden of rare predicted damaging variants would reduce scores for cognitive variables and increase scores for personality traits. The definition of the variant classes is given in Figure 1.