 Here the authors used an evidence-based strategy to prioritise causal pleiotropic variants of autoimmune diseases, and revealed that IS-4-7-2-8-1-4-2 modulates aberrant IRF-5 alternative promoter usage by ZBTB-3-mediated chromatin looping. This article was authored by Zhao Wang, Qian Liang, Xin Yiqian, and others.