Fig. 6: Schizophrenia polygenic risk predicts brain function and tracks PVALB expression.

a Genes were rank-ordered by cortical spatial correlation to SST and PVALB, then divided into 500-gene bins. MAGMA competitive gene set analysis revealed enrichment of polygenic risk for schizophrenia in the top PVALB (p = 0.022), but not the top SST (p = 0.51) set. Enrichment decreased across ordered bins for PVALB (Spearman’s r_s = −0.48, p = 0.03) but not for SST (Spearman’s r_s = −0.001, p = 0.51). b Schizophrenia polygenic risk negatively predicts RSFA within the visual (q_1.0 = 0.04) cluster, as well as somato/motor (q_1.0 = 0.08) and prefrontal (q_1.0 = 0.10) clusters at trend-levels (corrected for multiple-comparisons). c Parcel-wise prediction of RSFA by the schizophrenia PRS negatively correlated with cortical expression of PVALB (Pearson’s r = −0.33, p = 3.1e−10), which was also significant relative to all genes (PVALB = 145/17,448, AUC = 0.008). d Across all deconvolved cell type distributions, PVALB was the most negatively correlated to cortical SCZ-RSFA effects (frontal cortex: Pearson’s r(337) = −0.36, p = 9.5e−12; visual cortex: Pearson’s r(337) = −0.26, p = 9.0e−7). SCZ = schizophrenia; PRS = polygenic risk score; RSFA = resting state functional amplitude. *q ≤ 0.05. Error bars = standard error.