Fig. 7

Identification of SNPs predicted to influence TF binding affinity at GWAS loci in LOAD CCANs. a, Summary tables of SNP-TFBS overlaps in unidirectional and mixed LOAD CCANs. b–e, Diagrams of specific example SNP-TFBS overlaps. The cell subtype, regulated DEG, TF and SNP ID are shown in bold. The log fold change (Log₂FC) and significance value (FDR) are shown for each DEG and corresponding cCRE. Additionally, functional information for each DEG is provided. The effect of the SNP on the TFBS affinity change and corresponding FDR determined using atSNP (see Methods) are noted. CCAN stacked plots show peak coaccessibility scores, directionality of changes in DAP accessibility in LOAD (red = increased accessibility, blue = reduced accessibility), and degree of LOAD association for GWAS loci. All features are arranged along the same horizontal axis to indicate chromosomal position. cCRE stacked plots are detailed from boxed area of CCAN plots and additionally indicate overlapped gene coding regions, with upregulated DEGs shown in red and downregulated DEGs shown in blue, as well as normalized chromatin accessibility of the genomic region in LOAD and Normal samples. TFBS activity stacked plots are detailed from boxed areas of cCRE plots and indicate aligned chromosomal positions of TFBSs (Reference and disrupted TFBS—dark and light gold horizontal bars, respectively—were determined based on position weight matrix as described in Methods) and SNPs (black lettering). TF Network plots illustrate potential regulatory networks between DEG-overlapping peaks (blue) and TFBS-overlapping peaks (green), with those linkages predicted to be affected by LOAD SNPs shown in red