Fig. 6.
Gender-dependant PPP1R12B (top) or PPP1R1B (bottom) interactions with other genes in SUDs: (a) males; (b) females. 46 genes, organized in a wheel here in seven categories (enzyme, receptors, signalling, structure, TF, transporter and other; also listed in Supplementary Table 1), were included in this epistasis analysis. TF, transcription factors (e.g., HIVEP2 and unpublished PLAGL1); interacting genes are labelled in red; black triangle, known risk for SUDs, per reported meta-analyses (no interaction found for PD in this 46 genes-network (see Supplementary Fig. 2; also for the full labelling of genes). All interactions shown here reached statistical significance after Bonferroni correction and most of them reached absolute genome-wide significance (Pmeta<10−20), referring to the thermometer bar; FOXA1 SNPs might represent next gene TTC6 and ADH1B SNPs might represent next gene ADH1C too; scale bar, 100 kb. (c) Selective contribution of PPP1R12B (top) or PPP1R1B (bottom) to SUDs (top P value, from gender combined data), especially in females (P value grey-underlined, OR=6.7 (PPP1R12B) and 2.1 (PPP1R1B)) comparing to PD, based on number of statistically significant interactions; gender-specific selectivity for SUDs over PD: P = 1.6 × 10−28 in males and 4.1 × 10−178 (OR=164) in females in PPP1R12B and P = 5.9 × 10−23 (OR=50.8) in males and 4.7 × 10−49 in females in PPP1R1B.