Figure 8

Susceptibility-associated variation at rs11121129 disrupts an AP1 binding site associated with TNFRSF9 expression in neutrophils. (A) Top 10 binding sites ranked according to their enrichment with respect to sequences adjacent to genes co-expressed with TNFRSF9 in neutrophils. The listed binding sites include only those that are sensitive to variation at SNPs in linkage disequilibrium with rs11121129 (r ² > 0.90). The chart shows the Z statistic quantifying the degree to which each binding site is enriched among sequences adjacent to TNFRSF9-co-expressed genes. Associated p-values are listed in the left margin, where an asterisk symbol is used to denote FDR < 0.05. The right margin lists the SNP for which variation is predicted to influence binding. Blue font denotes binding sites for which the risk variant abrogates a match to the binding site, while red font denotes binding sites for which the risk variant engenders a match to the binding site. (B) Sequence logo for Fos|SWGNSNSMDG. The black arrow denotes the position for which variation at rs6687168 is predicted to influence binding (see parts D and E). (C) Sequence logo for CREL|BGGNNTTTCC|M00053. The black arrow denotes the position for which variation at rs6661746 is predicted to influence binding. (D) Top 10 binding sites matching the non-risk variant at rs6687168 (Chr 1, 8268893 – 8268933). (E) Top 10 binding sites matching the risk variant at rs6687168 (Chr 1, 8268893 – 8268933). In both (D) and (E), the right margin lists p-values quantifying the degree to which motifs are enriched among sequences adjacent to TNFRSF9-co-expressed genes in neutrophils.