a, The number of high confidence MS SNPs with a PICS
probability >0.5 in the genome, in all ATAC-seq peaks, or in
differentially accessible ATAC-seq peaks (for which the P value
was calculated with one-sided hypergeometric test). b, Top,
expression of genes surrounding MS SNP rs1465697 in CD4+ T cells.
Data are presented as mean ± s.d. Bottom, changes in
chromatin accessibility at rs1465697 and accompanying changes in
CD37 expression in KLF2, TNFAIP3 and ZNF217 knockouts.
ATAC-seq data are shown as normalized read coverage; samples were normalized
using the size factors from DESeq2. RNA-seq data are presented as the effect
size from Limma with error bars showing the 95% confidence interval.
c, Cartoon illustrating MS SNPs both at GATA3
and at a putative CRE upstream of RGS1. Changes in chromatin
accessibility at rs1323292 and accompanying changes in RGS1
expression in GATA3 knockout. ChIP–seq of GATA3 binding at rs1323292.
ATAC-seq data are shown as normalized read coverage; samples were normalized
using the size factors from DESeq2. ChIP–seq data are shown as background
subtracted binding in reads per million. RNA-seq data are presented as the
effect size from Limma, with error bars showing the 95% confidence interval.
chr, chromosome. d, A small subset of the regulatory connections
identified in this study between seed immune disease genes, their upstream
regulators and MS disease genes. This subnetwork is focused on regulators that
have a significant effect on CD37 or RGS1
chromatin accessibility and gene expression.
n = 3 donors for all RNA-seq and ATAC-seq data in
b and c. See also Extended Data Fig. 6.