Extended Data Fig. 9: Genome-wide CRISPRi screen targeting variants in accessible chromatin.

a, Library makeup of genome-wide screen. b, Screen workflow. c, Rank order plot depicting targets of the CRISPRi screen, with positive control genes VAV1, IL2RB, TBX21, and CBLB, other tested genes, and variants indicated by rsid. Targets with MAGeCK permutation test P-values that are FDR corrected using the Benjamini-Hochberg with a value of less than 0.1 are indicated in blue. d, Locus plot of the MYC locus showing two variants that are proliferation hits in the screen (rank of hit in blue) in a distal enhancer that contacts the MYC promoter as determined by pcHiC in T cells. e and f, comparison of proliferation effects of targeting CRISPRi to emVar-CREs and effects of ablating local V2G-associated genes in a genome-wide CRISPR screen66 (e) with (f) showing only the most significant V2G gene. g and h, The lymphocyte activation (g) and mRNA processing (h) clusters made up from the hits from the 56 emVar proliferation screen with each putative emVar target gene represented with color. i, Normalized counts of rs62136101 variant alleles tested in primary T cell MPRAs across 7 donors. Each line indicates one donor.