Fig. 5: Functional annotation of factor variants.

a, GO enrichment analysis of predicted target genes with transdiagnostic associations (that is, variants associated with the p-factor), or those target genes associated with the SB factor that were not overlapping with p-factor target genes. Depicted −log₁₀-transformed P values are one-sided, calculated using a χ² test; false-discovery rate (FDR) correction was applied for multiple comparisons. b, The averaged and normalized expression levels of target genes of the indicated classes along the temporal trajectory of human brain development. Shading around the lines reflects 95% CIs. pcw10, post-conception week 10. c,d, Average log₁₀[P] values across EWCE and MAGMA enrichment for genes associated with the indicated factors in fetal brain cell types using two independent single-cell RNA-sequencing (scRNA-seq) datasets^53,54 (c) or adult brain cell types using three independent single-nucleus RNA-seq (snRNA-seq) datasets^55,56,57 (d). The P values from EWCE and MAGMA were two-sided and each had an FDR correction applied for multiple comparisons before averaging the two sets of results. EWCE P values were empirically derived using a permutation test; MAGMA P values were calculated using an F-test. Int, Internalizing disorders factor. The implied sample size for the three depicted psychiatric factors was: SB (\(\hat{n}\) = 127,202), Internalizing (\(\hat{n}\) = 1,637,337) and p-factor (\(\hat{n}\) = 2,168,621). CycProg, cycling progenitor; Endo/BBB, endothelial/blood brain barrier; ExNeu, excitatory neuron; InNeu, interneurons; IP, intermediate progenitor; OPC, oligodendrocyte progenitor cell; RG, radial glia; Astro, astrocyte; MSN, medium spiny neuron; ODC/Oligo, oligodendrocyte.