Figure 1 |. Cohort description and transcriptomic analysis.

a, Representation of individuals in the hiPSC cohort used for this study (5’-NRXN1^+/− deletions in blue; 3’-NRXN1^+/− deletions in red; controls in gray) with schematic of the NRXN1 gene structure highlighting the exons encompassed by 5’-(blue) and 3’-(red) NRXN1^+/− deletions. b, Validation of hiPSC-derived neural cells by immunostaining for SOX2 and NESTIN (NPCs) and MAP2 (6-week hiPSC-neurons) with DAPI stained nuclei, 3 independent differentiations per line. c, Volcano plot showing log₂(foldchange) between NRXN1^+/− (18 samples, 4 donors) and controls (19 samples, 4 donors) and the –log₁₀(P-value) by linear model for each gene with FDR < 20% in red, FDR < 10% in orange and NRXN1 in blue. d, Gene set enrichment analysis, with –log₁₀(P-value) computed by Fisher Exact test using mSigDB⁶⁸. e, Concordance computed using Spearman correlation of the t-statistics between two datasets. Comparisons were made between this study and postmortem RNA-seq datasets of schizophrenia (SZ), major depressive disorder (MDD), bipolar disorder (BD), and autism spectrum disorder (ASD) from CommonMind³³, NIMH HBCC and UCLA⁶⁹. f, Sum of all NRXN1 transcript expression by cell type (19 samples, 8 donors hiPSC-NPC; 18 samples, 8 donors hiPSC-neurons) and genotype (19 samples, 4 donors controls; 10 samples, 2 donors 5’-NRXN1^+/−; 8 samples, 3 donors 3’-NRXN1^+/−). g,h, Differential isoform usage in hiPSC-neurons across genotypes (9 samples, 3 donors controls; 5 samples, 2 donors 5’-NRXN1^+/−; 5 samples, 2 donors 3’-NRXN1^+/−) when sub-setting for NRXN1α isoforms (g) or NRXN1β isoforms (h). Violin plots display median and quartiles (*P < 0.05, **P < 0.01 by one-way ANOVA with Dunnett’s Test). i, Gene set enrichments for genes correlated with NRXN1 spicing in hiPSC-neurons.