Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells.

ABSTRACT: Genome-wide association studies (GWASs) have uncovered hundreds of autoimmune disease-associated loci; however, the causal genetic variants within each locus are mostly unknown. Here, we perform high-throughput allele-specific reporter assays to prioritize disease-associated variants for five autoimmune diseases. By examining variants that both promote allele-specific reporter expression and are located in accessible chromatin, we identify 60 putatively causal variants that enrich for statistically fine-mapped variants by up to 57.8-fold. We introduced the risk allele of a prioritized variant (rs72928038) into a human T cell line and deleted the orthologous sequence in mice, both resulting in reduced BACH2 expression. Naive CD8 T cells from mice containing the deletion had reduced expressi

SUBMITTER: Mouri K 

PROVIDER: S-EPMC9793778 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature