| First Author | Mouri K | Year | 2022 |
| Journal | Nat Genet | Volume | 54 |
| Issue | 5 | Pages | 603-612 |
| PubMed ID | 35513721 | Mgi Jnum | J:332957 |
| Mgi Id | MGI:7378651 | Doi | 10.1038/s41588-022-01056-5 |
| Citation | Mouri K, et al. (2022) Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells. Nat Genet 54(5):603-612 |
| abstractText | 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 expression of genes that suppress activation and maintain stemness and, upon acute viral infection, displayed greater propensity to become effector T cells. Our results represent an example of an effective approach for prioritizing variants and studying their physiologically relevant effects. |
