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. Author manuscript; available in PMC: 2021 Apr 26.
Published in final edited form as: Nat Genet. 2020 Oct 26;52(11):1158–1168. doi: 10.1038/s41588-020-00721-x

Extended Data Fig. 7. Multi-omic characterization of well-studied AD-related GWAS loci pinpoints putative functional noncoding SNPs.

Extended Data Fig. 7

a,c, Normalized scATAC-seq-derived pseudo-bulk tracks, H3K27ac HiChIP loop calls, co-accessibility correlations, and publically available H3K4me3 PLAC-seq loop calls (Nott. et al. 2019) in (a) the BIN1 gene locus (chr2:127045000–127182000) and (c) the MS4A gene locus (chr11:60023000–60554000). scATAC-seq tracks represent the aggregate signal of all cells from the given cell type and have been normalized to the total number of reads in TSS regions, enabling direct comparison of tracks across cell types. For HiChIP, each line represents a FitHiChIP loop call connecting the points on each end. Red lines contain one anchor overlapping the SNP of interest while grey lines do not. For co-accessibility, only interactions involving the accessible chromatin region of interest are shown. For PLAC-seq, MAPS loop calls from microglia (blue), neurons (orange), and oligodendrocytes (purple) are shown. b,d, GkmExplain importance scores for each base in the 50-bp region surrounding (b) rs13025717 or (d) rs636317 for the effect and non-effect alleles from the gkm-SVM model for microglia (Cluster 24). The predicted motif affected by the SNP is shown at the bottom and the SNP of interest is highlighted in blue. e, Dot plot showing allelic imbalance at rs636317. Significance of allelic imbalance was determined by RASQUAL. The bulk ATAC-seq counts determined by WASP and ASEReadCounter for the reference/non-effect (A) allele and variant/effect (T) allele are plotted. Each dot represents an individual bulk ATAC-seq sample (N = 140) colored by the brain region from which the sample was collected. Samples where fewer than 3 reads were present to support both the reference and variant allele (i.e. presumed homozygotes or samples with insufficient sequencing depth) are shown in grey. The blue line represents a linear regression of the non-grey points and the grey box represents the 95% confidence interval of that regression.