Extended Data Fig. 1: Integrative genomic analysis of CH genetic risk.
a) Heatmap showing expression of CH risk genes across developmental timepoints and regions of the developing human brain. Analyzed transcriptomic dataset from12. b) Enrichment of CH risk genes across developmental timepoints of the human brain in a microarray dataset of the human brain from11. PCW: post-conception week, M: month, Y: year. Boxplot (in f): median (line), 25th and 75th percentiles (box), whiskers extend up to 1.5 times the interquartile range from the top (bottom) of the box to the furthest datum within that distance. Significance was calculated by comparing to background expression using one-sided Wilcoxon rank sum test. For detailed statistical information, see Supplementary Table 13. c-e) CH risk gene network connectivity in different layers of the prenatal human frontal neocortex. Analyzed transcriptomic dataset from13. c) VZ- and SVZi-specific CH risk gene interaction networks have the highest average connectivity per interaction. d-e) VZ (d) and SVZi (e) have significantly higher CH risk gene interaction network connectivity than expected by chance. The red line indicates the observed connectivity, and the gray histogram shows the null distribution from 1,000 permutations. P values were calculated by permutation tests (see Methods). f) Heatmap showing maximal expression of CH risk genes across different cell types of the developing human cortex. Analyzed transcriptomic dataset from12. g) Enrichment of CH risk genes in a prenatal human brain single-cell RNA sequencing data set from14. Purple square highlights lack of enrichment in choroid plexus cells. Choroid: choroid plexus, Glyc: glycolysis, IPC: intermediate progenitor cells, MGE: medial ganglionic eminence, OPC: oligodendrocyte precursor cells, RGC: radial glia cells. P values were calculated by hypergeometric test. h) Enrichment of CH risk genes in a postnatal mouse ventricular wall single-cell RNA sequencing data set from17. Purple square highlights lack of enrichment in ependymal cells. aNSC: actively dividing neural stem cells, TAC: transit amplifying cells, NB: neuroblasts, OPC: oligodendrocyte progenitor cells, COP: committed oligodendrocyte precursors. P values were calculated by hypergeometric test. i) Enrichment of CH risk genes in a prenatal mouse meninges single-cell RNA sequencing data set from18. P values were calculated by hypergeometric tests.
