biostudies-literatureMouri KHoward Hughes Medical InstituteNIAID NIH HHSNHGRI NIH HHSNINDS NIH HHSNIAMS NIH HHS603-612https://www.ebi.ac.uk/biostudies/studies/S-EPMC9793778biostudies-literatureUnknown54(5)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 expressiNature geneticsPrioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells.PMC9793778R01 AI151051K99 HG009920U01 AI142756DP2 AI183504K22 AI153648P50 HG006193R35 HG011329T32 AR007108F32 AI129249R25 NS065745R01 HG008131R00 HG008179UM1 HG009435R01 AI124693RM1 HG009490Gentili MRay JPLissner MMDeBerg HAGuo MHde Boer CGPlatt WFCampbell DJHacohen NMouri KTewhey RLiu DRNewby GAHarten IAfalsePrioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells.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 expressi2022-01-01T00:00:00Z2022 May2026-05-31T15:54:17.44Z2025-04-04T12:45:46.675ZS-EPMC97937783551372110.1038/s41588-022-01056-5