Extended Data Fig. 8: Regulatory mechanisms of GWAS identified noncoding variants.
From: Complementary Alu sequences mediate enhancer–promoter selectivity
a–b, The overlapped variant-gene pairs between GWAS variants-to-function maps and the maps built by EpiMap, ENCODE, or ABC model across all biosamples (a) and the 7 cell types (b) used in our study. c–d, Distribution of EPRI chimeric reads around DHSs located at enhancers (c) and promoters (d). e–f, GRO-seq signals around DHSs located at enhancers (e) and promoters (f) in HeLa cells. g, Mapping GWAS-associated noncoding variants into EPRI map to construct a variant-to-function map. Mutated Alus in enhancers or promoters are shown as red triangles and circles. h, Enriched KEGG pathways for the affected genes in panel g. i, GWAS variant rs6914598 in SE1838 is linked to the promoter of BCAT2. j, The rs9269081 in TE19551 is linked to the promoter of HLA-DRB5. Orange and green boxes represent enhancers and promoters (Pro.). k,l, RBP-binding profiles around the interacting enhancer and promoter RNA fragments in K562 (k) and HepG2 cells (l). The color scale indicates normalized complexity. m, Schematic diagram of Jaccard similarity index used to analyze RBPs co-bound at interacting eRNAs and uaRNAs (or promoter RNAs). n,o, Boxplot showing EPRIs have a higher Jaccard index (red box) than randomly paired enhancers and promoters (blue box) in K562 (n) and HepG2 cells (o). The center line of the box plot represents the median, the box borders represent the first (Q1) and third (Q3) quartiles, and the whiskers are the most extreme data points within 1.5× the interquartile range (from Q1 to Q3). P-values are determined by a two-tailed unpaired Student’s t-test. EPRI chimeric reads are 47,876 and 30,181 for K562 and HepG2 cells, respectively. p,q, SNVs were preferentially positioned around the eCLIP peaks for RBPs enriched on eRNAs and uaRNAs in K562 (p) and HepG2 cells (q).
