Fig. 4: Expression of ADHD risk genes across brain developmental stages and cell types.
From: Rare genetic variants confer a high risk of ADHD and implicate neuronal biology
a, Mean expression, expressed as ln(reads per kilobase million (RPKM) + 1)), of the 17 ADHD risk genes and background genes across neocortical brain developmental stages in BrainSpan. Background genes (22,402 genes or transcripts) include genes expressed in BrainSpan, except for the 17 ADHD risk genes. Asterisks indicate a significant difference between the two gene sets at a given developmental stage using a two-sided paired t-test or Wilcoxon rank test; P = 4.17 × 10−3 was considered significant, correcting for 12 brain developmental stages. Vertical lines represent standard error. b, Expression of the three significant genes across brain developmental stages, and expression of background genes (22,416 genes or transcripts). Asterisks next to the gene names at the right side indicate significant differences in mean prenatal and postnatal expression using a two-sided two-sample t-test; P = 2.2 × 10−16 (MAP1A) and P = 2.2 × 10−16 (ANO8); two-sided P = 1.67 × 10−2 was considered significant, correcting for three comparisons. Vertical lines represent standard error. Sample sizes for each neocortical brain developmental stage are in Supplementary Table 12. c, Top, uniform manifold approximation and projection (UMAP) of scRNA-seq data32, showing clustering of cell types from human iPS cell cultures developed towards midbrain neuronal cell types. Results are shown for cells developed for 11, 30 and 52 days: astrocyte-like (Astro), dopaminergic neurons (DA), ependymal-like 1 (Epen1), ependymal-like 2 (Epen2), floor-plate progenitors (FPP), neuroblasts (NB), proliferating floor-plate progenitors (P_FPP), proliferating serotonergic-like neurons (P_Sert), serotonergic-like neurons (Sert), unknown neuron 1 (U_Neur1), unknown neuron 2 (U_Neur2) and unknown neuron 3 (U_Neur3). Bottom, scDRS for each cell, with the strength indicated by the bar on the right. Red or blue indicates a positive or a negative score, respectively, reflecting increased or decreased expression of ADHD rare-variant risk genes compared with the distribution of expression of control gene sets in a cell.
